Name (Synonyms) | Correlation | |
---|---|---|
drug108 | Azithromycin Wiki | 0.39 |
drug850 | Placebo Wiki | 0.22 |
drug865 | Placebo oral tablet Wiki | 0.20 |
drug1255 | Zinc Wiki | 0.19 |
drug1230 | Vitamin C Wiki | 0.18 |
drug431 | Favipiravir Wiki | 0.17 |
drug645 | Lopinavir-Ritonavir Wiki | 0.15 |
drug1135 | Telmisartan Wiki | 0.15 |
drug1258 | Zinc Sulfate Wiki | 0.15 |
drug1012 | Sarilumab Wiki | 0.13 |
drug647 | Lopinavir/ritonavir Wiki | 0.13 |
drug586 | Interferon Beta-1A Wiki | 0.13 |
drug587 | Interferon Beta-1B Wiki | 0.13 |
drug1168 | Tocilizumab Wiki | 0.12 |
drug60 | Anakinra Wiki | 0.12 |
drug1256 | Zinc (Placebo) Wiki | 0.11 |
drug56 | Alvelestat (MPH996) Plus Aerosolized 13 cis retinoic acid Wiki | 0.11 |
drug1202 | Ultra-Low-dose radiotherapy Wiki | 0.11 |
drug250 | Ceftriaxone Wiki | 0.11 |
drug1204 | Umbilical Cord Mesenchymal Stem Cells Wiki | 0.11 |
drug1279 | blood samples Wiki | 0.11 |
drug311 | Convalescent Plasma 1 Unit Wiki | 0.11 |
drug699 | Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) Wiki | 0.11 |
drug849 | Piperacillin/tazobactam Wiki | 0.11 |
drug1259 | Zithromax Oral Product Wiki | 0.11 |
drug1090 | Sterile Normal Saline for Intravenous Use Wiki | 0.11 |
drug648 | Lopinavir/ritonavir 400 mg/100 mg Wiki | 0.11 |
drug1401 | standard procedure Wiki | 0.11 |
drug676 | Mannitol Wiki | 0.11 |
drug101 | Aviptadil (VIP) Wiki | 0.11 |
drug317 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.11 |
drug472 | HCQ + Placebo Wiki | 0.11 |
drug511 | Hydroxychloroquine + azithromycin + / - tocilizumab Wiki | 0.11 |
drug861 | Placebo of Hydroxychloroquine Wiki | 0.11 |
drug3 | - Synthetic anti-malarial drugs Wiki | 0.11 |
drug334 | Cytokine Adsorption Wiki | 0.11 |
drug1183 | Treatment with Dexmedetomidine Wiki | 0.11 |
drug78 | Apple Watch Series 5 Wiki | 0.11 |
drug1153 | There is no intervention in this study Wiki | 0.11 |
drug870 | Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki | 0.11 |
drug654 | Low molecular weight heparin Wiki | 0.11 |
drug385 | ECCO2R Wiki | 0.11 |
drug644 | Lopinavir and ritonavir Wiki | 0.11 |
drug575 | Indomethacin Wiki | 0.11 |
drug1233 | Vitamins Wiki | 0.11 |
drug1075 | Standard supportive care Wiki | 0.11 |
drug442 | Fixed-duration Hydrocortisone Wiki | 0.11 |
drug471 | HCQ + Intravenous Famotidine Wiki | 0.11 |
drug312 | Convalescent Plasma 2 Units Wiki | 0.11 |
drug938 | Radiation therapy Wiki | 0.11 |
drug1147 | The standard Macintosh laryngoscope Wiki | 0.11 |
drug753 | Nitazoxanide 500 MG Wiki | 0.11 |
drug512 | Hydroxychloroquine + lopinavir/ritonavir Wiki | 0.11 |
drug9 | 1: ILT101 Wiki | 0.11 |
drug411 | Enriched Survey Feedback Wiki | 0.11 |
drug1032 | Shock-dependent hydrocortisone Wiki | 0.11 |
drug105 | Ayurveda Wiki | 0.11 |
drug592 | Interferon-β1a Wiki | 0.11 |
drug1386 | remdesivir Wiki | 0.11 |
drug1068 | Standard of care (SOC) Wiki | 0.11 |
drug124 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.11 |
drug711 | Moxifloxacin or Levofloxacin Wiki | 0.11 |
drug1069 | Standard of care management Wiki | 0.11 |
drug862 | Placebo of LPV/r Tablets Wiki | 0.11 |
drug812 | PEEP trial Wiki | 0.11 |
drug507 | Hydroxychloroquine (placebo) Wiki | 0.11 |
drug537 | Hydroxychloroquine and azithromycin treatment arm. Wiki | 0.11 |
drug854 | Placebo Administration Wiki | 0.11 |
drug1420 | ventilatory support with oxygen therapy Wiki | 0.11 |
drug675 | Macrolide administered for up to 14 days Wiki | 0.11 |
drug225 | COVID-19 test, polymerase chain reaction for SARS-CoV-2 Wiki | 0.11 |
drug305 | Control arm Wiki | 0.11 |
drug364 | Dexamethasone and Hydroxychloroquine Wiki | 0.11 |
drug455 | Gargle/Mouthwash Wiki | 0.11 |
drug1302 | eculizumab Wiki | 0.11 |
drug689 | Mefloquine + azithromycin + / - tocilizumab Wiki | 0.11 |
drug2 | (Standard of Care) SoC Wiki | 0.11 |
drug1157 | Thoracic CT Scan Wiki | 0.11 |
drug559 | IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki | 0.11 |
drug443 | Fixed-duration higher dose Hydrocortisone Wiki | 0.11 |
drug1416 | trimethoprim/sulfamethoxazole Wiki | 0.11 |
drug327 | Corticosteroid Wiki | 0.11 |
drug737 | Naltrexone Wiki | 0.11 |
drug272 | Ciclesonide Metered Dose Inhaler [Alvesco] Wiki | 0.11 |
drug642 | Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki | 0.11 |
drug638 | Lopinavir / Ritonavir Pill Wiki | 0.11 |
drug254 | Centricyte 1000 Wiki | 0.11 |
drug1038 | Sirolimus 1 MG/ML Wiki | 0.11 |
drug632 | Liberase Enzyme (Roche) Wiki | 0.11 |
drug1098 | Study Group Wiki | 0.11 |
drug1262 | additional blood tubes Wiki | 0.11 |
drug832 | Peer Resilience Champion Wiki | 0.11 |
drug458 | Gimsilumab Wiki | 0.11 |
drug52 | Alteplase 100 MG [Activase] Wiki | 0.11 |
drug59 | Amoxicillin-clavulanate Wiki | 0.11 |
drug375 | Dociparastat sodium Wiki | 0.11 |
drug871 | Placebo: Hydroxychloroquine Wiki | 0.11 |
drug441 | Five-days oseltamivir Wiki | 0.11 |
drug1276 | blood donation SMS Wiki | 0.11 |
drug366 | Dexmedetomidine Injectable Product Wiki | 0.11 |
drug328 | Corticosteroid injection Wiki | 0.11 |
drug235 | CYNK-001 Wiki | 0.11 |
drug1337 | mRNA-1273 Wiki | 0.11 |
drug249 | Ceftaroline Wiki | 0.11 |
drug535 | Hydroxychloroquine and Ivermectin Wiki | 0.11 |
drug1231 | Vitamin D Wiki | 0.11 |
drug93 | Association of diltiazem and niclosamide Wiki | 0.11 |
drug367 | Diagnosis of SARS-Cov2 by RT-PCR and : IgG, Ig M derologies in the amniotoc fluid, the blood cord and the placenta Wiki | 0.11 |
drug574 | Individualised Ayurveda Wiki | 0.11 |
drug618 | Ketamine Wiki | 0.11 |
drug277 | Clevudine Wiki | 0.11 |
drug140 | Baricitinib Wiki | 0.11 |
drug239 | Camostat Mesilate Wiki | 0.11 |
drug674 | Macrolide administered for 3-5 days Wiki | 0.11 |
drug1057 | Standard Plasma (FFP) Wiki | 0.11 |
drug492 | High-Titer COVID-19 Convalescent Plasma (HT-CCP) Wiki | 0.11 |
drug848 | Piperacillin-tazobactam Wiki | 0.11 |
drug53 | Alteplase 50 MG [Activase] Wiki | 0.11 |
drug799 | Oral placebo Wiki | 0.11 |
drug382 | Duodenal biopsy Wiki | 0.11 |
drug1008 | Saliva Wiki | 0.11 |
drug893 | Practice details Wiki | 0.11 |
drug1180 | Transpulmonary thermodilution Wiki | 0.11 |
drug404 | Emtricitabine/tenofovir disoproxil Wiki | 0.11 |
drug688 | Mefloquine Wiki | 0.11 |
drug1146 | The Vie Scope laryngoscope Wiki | 0.11 |
drug584 | Injective placebo Wiki | 0.11 |
drug16 | 2: Placebo Comparator Wiki | 0.11 |
drug1138 | Ten-days oseltamivir Wiki | 0.11 |
drug977 | Ruxolitinib Wiki | 0.08 |
drug393 | Echocardiography Wiki | 0.08 |
drug379 | Doxycycline Wiki | 0.08 |
drug565 | Imatinib Wiki | 0.08 |
drug510 | Hydroxychloroquine + azithromycin Wiki | 0.08 |
drug450 | GLS-5300 Wiki | 0.08 |
drug534 | Hydroxychloroquine and Azithromycin Wiki | 0.08 |
drug775 | Normal saline Wiki | 0.08 |
drug532 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.08 |
drug976 | Routine care for COVID-19 patients Wiki | 0.08 |
drug533 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.08 |
drug378 | Dornase Alfa Inhalation Solution [Pulmozyme] Wiki | 0.08 |
drug1020 | Selinexor Wiki | 0.08 |
drug264 | Chloroquine Sulfate Wiki | 0.08 |
drug508 | Hydroxychloroquine + Azithromycin Wiki | 0.08 |
drug957 | Remdesivir Wiki | 0.07 |
drug1062 | Standard of Care Wiki | 0.07 |
drug1067 | Standard of care Wiki | 0.07 |
drug874 | Plasma Wiki | 0.06 |
drug637 | Lopinavir / Ritonavir Wiki | 0.06 |
drug1082 | Standard treatment Wiki | 0.06 |
drug872 | Placebos Wiki | 0.05 |
drug1211 | Usual Care Wiki | 0.05 |
drug1280 | blood sampling Wiki | 0.05 |
drug801 | Oseltamivir Wiki | 0.05 |
drug612 | Ivermectin Wiki | 0.04 |
drug262 | Chloroquine Wiki | 0.04 |
drug923 | Questionnaire Wiki | 0.04 |
drug762 | No intervention Wiki | 0.04 |
Name (Synonyms) | Correlation | |
---|---|---|
D003141 | Communicable Diseases NIH | 0.32 |
D007239 | Infection NIH | 0.28 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.27 |
D055371 | Acute Lung Injury NIH | 0.25 |
D018352 | Coronavirus Infections NIH | 0.24 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.23 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.22 |
D013577 | Syndrome NIH | 0.13 |
D003333 | Coronaviridae Infections NIH | 0.13 |
D011024 | Pneumonia, Viral NIH | 0.11 |
D030341 | Nidovirales Infections NIH | 0.11 |
D011649 | Pulmonary Alveolar Proteinosis NIH | 0.11 |
D009410 | Nerve Degeneration NIH | 0.11 |
D055370 | Lung Injury NIH | 0.11 |
D012213 | Rheumatic Fever NIH | 0.11 |
D001987 | Bronchiectasis NIH | 0.11 |
D004660 | Encephalitis NIH | 0.11 |
D012327 | RNA Virus Infections NIH | 0.11 |
D054990 | Idiopathic Pulmonary Fibrosis NIH | 0.11 |
D017250 | Caliciviridae Infections NIH | 0.11 |
D000071257 | Emergence Delirium NIH | 0.11 |
D014777 | Virus Diseases NIH | 0.11 |
D011014 | Pneumonia NIH | 0.09 |
D008171 | Lung Diseases, NIH | 0.09 |
D007154 | Immune System Diseases NIH | 0.08 |
D018754 | Ventricular Dysfunction NIH | 0.08 |
D003693 | Delirium NIH | 0.08 |
D012216 | Rheumatic Diseases NIH | 0.08 |
D018487 | Ventricular Dysfunction, Left NIH | 0.08 |
D058070 | Asymptomatic Diseases NIH | 0.08 |
D011020 | Pneumonia, Pneumocystis NIH | 0.08 |
D003095 | Collagen Diseases NIH | 0.08 |
D012141 | Respiratory Tract Infections NIH | 0.07 |
D014947 | Wounds and Injuries NIH | 0.07 |
D000077062 | Burnout, Psychological NIH | 0.06 |
D011658 | Pulmonary Fibrosis NIH | 0.06 |
D001172 | Arthritis, Rheumatoid NIH | 0.06 |
D001327 | Autoimmune Diseases NIH | 0.06 |
D012769 | Shock, NIH | 0.05 |
D017563 | Lung Diseases, Interstitial NIH | 0.05 |
D004417 | Dyspnea NIH | 0.05 |
D001168 | Arthritis NIH | 0.04 |
D012140 | Respiratory Tract Diseases NIH | 0.03 |
D007249 | Inflammation NIH | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002383 | Encephalitis HPO | 0.11 |
HP:0002110 | Bronchiectasis HPO | 0.11 |
HP:0002180 | Neurodegeneration HPO | 0.11 |
HP:0006517 | Alveolar proteinosis HPO | 0.11 |
HP:0002090 | Pneumonia HPO | 0.09 |
HP:0002088 | Abnormal lung morphology HPO | 0.09 |
HP:0011947 | Respiratory tract infection HPO | 0.07 |
HP:0002206 | Pulmonary fibrosis HPO | 0.06 |
HP:0002960 | Autoimmunity HPO | 0.06 |
HP:0001370 | Rheumatoid arthritis HPO | 0.06 |
HP:0006515 | Interstitial pneumonitis HPO | 0.05 |
HP:0002098 | Respiratory distress HPO | 0.05 |
HP:0001369 | Arthritis HPO | 0.04 |
There are 85 clinical trials
REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome ofon patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.
Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and outside of ICU Time: Day 21Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 monthsDescription: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Measure: Destination at time of hospital discharge Time: Free text Day 90Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital dischargeDescription: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital dischargeDescription: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.
Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death Time: Day 90, censored at hospital dischargeDescription: Antiviral Domain specific outcome. Only required at selected sites.
Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens Time: Day 3, up to Day 7Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint
Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing) Time: Day 90, censored at hospital dischargeThe study aims to evaluate the efficacy and safety of hydroxychloroquine in the treatment of COVID-19 pneumonia.
Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.
Measure: The critical illness rate of subjects at weeks 2 Time: 14 days after randomizationStudy Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Description: Number of participants at 14 days post enrollment with active COVID19 disease.
Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline Time: 14 daysDescription: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline Time: 14 daysDescription: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measure: Incidence of Hospitalization Time: 14 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Measure: Incidence of Confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Measure: Incidence of Symptoms Compatible with COVID19 (possible disease) Time: 90 daysDescription: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal Time: 14 daysDescription: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall symptom severity at 5 and 14 days Time: 5 and 14 daysDescription: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.
Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry Time: 14 daysDouble blinded randomized clinical trial designed to evaluate the security and efficacy of hydroxychloroquine as treatment for COVID-19 severe respiratory disease. The investigators hypothesize that a 400mg per day dose of hydroxychloroquine for 10 days will reduce all-cause hospital mortality in patients with severe respiratory COVID-19 disease.
Description: incidence of all-cause mortality
Measure: All-cause hospital mortality Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: Days from ER admission to hospital discharge
Measure: Length of hospital stay Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: need of invasive or non invasive mechanical ventilation
Measure: Need of mechanical ventilation Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: 28 minus days without invasive ventilation support in patients with invasive mechanical ventilation at randomization
Measure: Ventilator free days Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: Adverse Reactions
Measure: Grade 3-4 adverse reaction Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysThis study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine. Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.
Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale Time: Day 15Description: Time to an improvement of one category from admission on an ordinal scale. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.
Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale Time: Days 3, 5, 8, 11, 15 and 29Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.
Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Time: Days 3, 5, 8, 11, 15 and 29Description: • Duration of hospitalization (days).
Measure: Hospitalization Time: 29 daysDescription: Rate of mortality
Measure: Mortality Time: In hospital, Day 28, Day 90Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of lopinavir Time: Days 1, 3, 5, 8 and 11Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of hydroxychloroquine Time: Days 1, 3, 5, 8 and 11Triple blinded, phase III randomized controlled trial with parallel groups (200mg of hydroxychloroquine per day vs. placebo) aiming to prove hydroxychloroquine's security and efficacy as prophylaxis treatment for healthcare personnel exposed to COVID-19 patients.
Description: Symptomatic infection rate by COVID-19 defined as cough, dyspnea, fever, myalgia, arthralgias or rhinorrhea along with a positive COVID-19 real-time polymerase chain reaction test.
Measure: Symptomatic COVID-19 infection rate Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startDescription: Symptomatic infection rate by other non-COVID-19 viral etiologies defined as cough, dyspnea, fever, myalgia, arthralgias or rhinorrhea along with a positive viral real time polymerase chain reaction test.
Measure: Symptomatic non-COVID viral infection rate Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startDescription: Number of days absent from labor due to COVID-19 symptomatic infection
Measure: Days of labor absenteeism Time: From date of randomization until study completion 60 days after treatment startDescription: Absenteeism from labor rate due to COVID-19 symptomatic infection
Measure: Rate of labor absenteeism Time: From date of randomization until study completion 60 days after treatment startDescription: Rate of severe respiratory COVID-19 disease in healthcare personnel
Measure: Rate of severe respiratory COVID-19 disease in healthcare personnel Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startThe purpose of this study is to test the hypothesis that post-exposure prophylaxis with hydroxychloroquine will reduce the symptomatic secondary attack rate among household contacts of known or suspected COVID-19 patients.
Description: This is defined as either 1. COVID-19 infection confirmed within 14 days of enrollment, following self-report of COVID-19 symptoms to the research study; OR, 2. COVID-19 infection confirmed within 14 days of enrollment, with self-report of COVID-19 symptoms to a treating physician.
Measure: Number of participants with symptomatic, lab-confirmed COVID-19. Time: Date of enrollment to 14 days post-enrollment dateThe Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.
Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: All-cause mortality rates at 29 days after randomization
Measure: All-cause mortality Time: 29 days after randomizationDescription: Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 7 and 29 days after randomizationDescription: Number of days free from mechanical ventilation at 29 days after randomization
Measure: Number of days free from mechanical ventilation Time: 29 days after randomizationDescription: Number of days that the patient was on mechanical ventilation after randomization
Measure: Duration of mechanical ventilation Time: 7, 15 and 29 days after randomizationDescription: Length of hospital stay on survivors
Measure: Duration of hospitalization Time: 7, 15 and 29 days after randomizationDescription: Presence of other secondary infections
Measure: Other secondary infections Time: 7, 15 and 29 days after randomizationDescription: Time from treatment start to death
Measure: Time from treatment start to death Time: 7, 15 and 29 days after randomizationDescription: Occurrence of QT interval prolongation
Measure: QT interval prolongation Time: 7, 15 and 29 days after randomizationDescription: Occurrence of gastrointestinal intolerance
Measure: Gastrointestinal intolerance Time: 7, 15 and 29 days after randomizationDescription: Occurrence of laboratory albnormalities in red blood cell count, creatinine and bilirubin
Measure: Laboratory albnormalities Time: 7, 15 and 29 days after randomizationDescription: Occurrence of adverse events related to the use of the investigational products
Measure: Adverse events Time: 7, 15 and 29 days after randomizationThe (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.
Description: All cause in-hospital mortality
Measure: In-hospital mortality Time: 3 weeksThis study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.
Description: The patient will becategorized into one of the following 8 categories depending on status of their hospitalization: Dead (yes/no) Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) Hospitalized and receiving Non-invasive ventilation or "high-flow oxygen device" (yes/no) Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) Hospitalized for observation (yes/no) Discharged from hospital with restriction of activity level (yes/no) Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be "yes".
Measure: Categorization of hospitalization status Time: 14 daysDescription: Delta PaO2 measured in arterial puncture
Measure: Change in patient's oxygen partial pressure Time: 4 daysDescription: Delta PaCO2 measured in arterial puncture
Measure: Change in patient's carbondioxid partial pressure Time: 4 daysDescription: pH measured in arterial puncture
Measure: Level of pH in blood Time: 4 daysA new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.
Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14 Time: Day 14Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28. Time: Day 28Since December 2019, the emergence of a new coronavirus named SARS-Cov-2 in the city of Wuhan in China has been responsible for a major epidemic of respiratory infections, including severe pneumonia. Within weeks, COVID-19 became a pandemic. In the absence of specific antiviral treatment, a special attention should be given to prevention. Personal protection equipments may be insufficiently protective, including in healthcare workers, a significant proportion of whom (around 4%) having been infected in the outbreaks described in China and more recently in Italy. Infection in healthcare workers could result from the contact with COVID-19 people in community or with infected colleagues or patients. As it will take at least a year before vaccines against SARS-CoV-2 becomes available, chemoprophylaxis is an option that should be considered in this setting where prevention of SARS-CoV-2 infection in Health Care Workers. The COVIDAXIS trial evaluates a chemoprophylaxis of SARS-CoV-2 infection in Health Care Workers. This trial is divided into two distinct studies that could start independently each with its own randomization process: COVIDAXIS 1 will study Hydroxychloroquine (HCQ) versus placebo; COVIDAXIS 2 will study Lopinavir/ritonavir (LPV/r) versus placebo. Upon randomization healthcare workers (HCWs) involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:
Description: An infection by SARS-CoV-2 is defined by either: a positive specific Reverse Transcription - Polymerase Chain Reaction (RT-PCR) on periodic systematic nasopharyngeal swab during follow-up OR a positive specific RT-PCR on a respiratory sample in case of onset of symptoms consistent with COVID-19 during follow-up OR a seroconversion to SARS-CoV-2 after randomization.
Measure: Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs) Time: Up to 2.5 monthsDescription: Number of adverse events expected or unexpected, related and unrelated to the treatment, notably grades 2, 3 and 4 (moderate, severe and lifethreatening, according to the Adverse National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0) in each arm.
Measure: Evaluation of the occurrence of adverse events in each arm, Time: Up to 2.5 monthsDescription: Number of treatment discontinuations in each arm
Measure: Evaluation of the discontinuation rates of the investigational drug in each arm, Time: Up to 2 monthsDescription: Treatment adherence rate will be assessed by: measurement of LPV and HCQ plasma concentrations using LC-MS/MS or LC-Fluorimetric detection the count of returned drugs at each visit.
Measure: Evaluation of the adherence of participants to study drug, Time: Up to 2 monthsDescription: Number of incident cases of symptomatic SARS-CoV-2 infections among HCWs in each arm. Symptomatic infection is defined as : a positive specific RT-PCR on a respiratory or non respiratory sample OR a thoracic CT scan with imaging abnormalities consistent with COVID-19. These investigations being performed in case of signs/symptoms consistent with COVID-19 during follow-up.
Measure: Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm, Time: Up to 2.5 monthsDescription: Number of incident cases of asymptomatic SARS-CoV-2 infection among HCWs in each randomization arm. Asymptomatic infection is defined as : a positive specific RT-PCR on periodic systematic nasopharyngeal swab during clinical follow-up without consistent clinical signs/symptoms during follow-up OR as seroconversion to SARS-CoV-2 between start and end of the study in HCWs that did not reported any consistent clinical symptoms during follow-up
Measure: Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm Time: Up to 2.5 monthsDescription: Number of incident cases of severe SARS-CoV-2 infections among HCWs in each randomization arm, defined as : a positive specific RT-PCR on a respiratory sample OR a thoracic CT scan with imaging abnormalities consistent with COVID-19 performed in case of onset of symptoms consistent with COVID-19 during follow-up in a participant who need to be hospitalized for respiratory distress. Respiratory distress defined as dyspnea with a respiratory frequency > 30/min, blood oxygen saturation <93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 and/or lung infiltrates >50% (1).
Measure: Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm. Time: Up to 2.5 monthsDescription: Safety. Electrocardiogram (ECG)
Measure: corrected QT interval (ms) Time: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.
Measure: COVID-19-free survival Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-CoV-2 detection Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
Measure: Incidence of possible COVID-19 symptoms Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: up to 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.
Measure: Incidence of study medication-related side effects Time: up to 12 weeksAlbertans with COVID-19 are at risk of deteriorating and developing severe illness. Those over age 40 or with co-morbid illness, and likely those who are immune suppressed, are at highest risk. This study will include a focus on people with immune-suppressed states. Individuals confirmed to have SARS-CoV-2 infection will be identified using administrative data (positive lab result, age 18 or over, not hospitalized, and not living in SL4 level of care). They will then be contacted by AHS staff, independent of the researchers, to obtain their consent for the researchers to contact them about this trial. The AHS staff member who contacts the individual will enroll consenting individuals into a study database. If they provided an email address an email will automatically be sent to the individual with study information. Those who decline to be contacted will also be informed of the study website so they can choose to review the study information and self-enrol, although they will need to do so quickly to meet study timelines. Enrolled participants will be contacted by a study coordinator. Those without access to the internet will be informed about the study details when they are contacted by a study coordinator. When the study coordinator contacts potential participants the study will be reviewed, and the potential participant will have an opportunity to ask questions. Consent for participation will be obtained by telephone. Telephone consent will be recorded. Participants will then be screened for inclusion and exclusion criteria by telephone interview and review of Alberta Netcare. Alberta Netcare is the province of Alberta's public Electronic Health Record used to store patient information so that it is easily accessible to healthcare professionals for the purpose of care. Information like immunizations, ECG results, diagnostic images and reports, written medical reports (e.g. surgery reports, consultations, hospital admissions), diagnostic lab testing results (e.g. blood tests, urine tests, blood bank info), allergies and intolerances (drug and food allergies, food intolerances), prescription history, and general patient information (e.g. name, birthdate, personal health number, address, phone number). Those who are not eligible for the study will be informed of the reason(s) for ineligibility (generally it will be a safety exclusion and they should be aware of this). Those who are eligible will be randomized to receive HCQ or placebo for a total duration of 5 days. Study drug will be delivered to their residence by courier. Telephone follow-up will occur at day 7 (range 7-10 days) and at day 30 (range 25-35 days).
Description: The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.
Measure: Composite of hospitalization, invasive mechanical ventilation or death within 30 days Time: Within 30 days of randomizationDescription: Mortality within 30 days of randomization
Measure: mortality Time: Within 30 days of randomizationDescription: defined as the number of days from randomization to complete symptom resolution, based on public health follow-up and day 7 and day 30 telephone interview (continuous)
Measure: Symptom duration Time: Within 30 days of randomizationDescription: Disposition of the patient at the Day 30 telephone followup
Measure: Disposition at 30 days defined as recovered, ongoing symptoms but not hospitalized, hospitalized, or deceased (categorical) Time: Within 30 days of randomizationAccording to In vitro studies, ciclesonide showed good antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some cases were reported for the clinical effectiveness of ciclesonide in the treatment of COVID-19, there is no clinical trial to evaluate the antiviral effect on the reduction of viral load in patients with COVID-19. In this study, we aimed to investigate whether ciclesonide alone or in combination with hydroxychloroquine could eradicate SARS-CoV-2 from respiratory tract earlier in patients with mild COVID-19.
Description: Viral load
Measure: Rate of SARS-CoV-2 eradication at day 14 from study enrollment Time: Hospital day 14Description: Viral load
Measure: Rate of SARS-CoV-2 eradication at day 7 from study enrollment Time: Hospital day 7Description: Viral load
Measure: Time to SARS-CoV-2 eradication (days) Time: Hospital day 1, 4, 7, 10, 14, 21Description: Viral load change
Measure: Viral load area-under-the-curve (AUC) reduction versus control Time: Hospital day 1, 4, 7, 10, 14, 21Description: Resolution of all systemic and respiratory symptoms for ≥2 consecutive days
Measure: Time to clinical improvement (days) Time: Up to 28 daysDescription: ICU admission, mechanical ventilation or death
Measure: Proportion of clinical failure Time: Up to 28 daysDescription: Number of adverse events, proportion of early discontinuance
Measure: Safety and tolerability of study drug Time: Up to 28 daysThis study is an adaptive, randomized, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization. Subjects will be randomized to receive either standard-of-care products or the study medication plus standard of care, while being hospitalized for COVID-19. Participants will be randomized to one of the following groups: 1. Lopinavir/ritonavir 400mg/100mg PO BID for 14 day plus optimized supportive care, OR 2. Hydroxychloroquine 800mg BID for 1 day then 400mg BID for 10 days plus optimized supportive care, OR 3. Remdesivir 200mg IV on day 1, followed by 100 mg IV daily infusion for 9 days plus optimized supportive care, OR 4. Optimized support care all or until discharge from hospital, whichever occurs first
Description: All-cause mortality, assessed at hospital discharge.
Measure: Efficacy of Interventions as assessed by all-cause mortality Time: 29 daysDescription: Measure with Ordinal Scale the time it takes for subject improvement
Measure: Time to improvement of one category from admission Time: up to 60 daysDescription: Subject clinical status at days 3, 5, 8, 11, 15, 29, 60 measured using the ordinal scale below: The scale is as below 0: Uninfected, no viral RNA Asymptomatic, viral RNA detected Symptomatic, independent Symptomatic, Assistance Needed Hospitalized: no oxygen therapy Hospitalized, on oxygen Hospitalized, Oxygen by NIV or high-flow Mechanical ventilation, p/f>150 or s/f >200 Mechanical ventilation, p/f<150 or s/f<200 OR vasopressors mechanical ventilation, p/f<150 AND vasopressors, dialysis, or ECMO death
Measure: Subject clinical status Time: up to 60 daysDescription: Mean change in the ranking from baseline to days 3, 5, 8, 11, 15, 29, 60 using the ordinal scale below: The scale is as below 0: Uninfected, no viral RNA Asymptomatic, viral RNA detected Symptomatic, independent Symptomatic, Assistance Needed Hospitalized: no oxygen therapy Hospitalized, on oxygen Hospitalized, Oxygen by NIV or high-flow Mechanical ventilation, p/f>150 or s/f >200 Mechanical ventilation, p/f<150 or s/f<200 OR vasopressors mechanical ventilation, p/f<150 AND vasopressors, dialysis, or ECMO death
Measure: Change in Subject clinical status Time: up to 60 daysDescription: the number of oxygen free days experienced
Measure: Oxygen free days Time: up to 29 daysDescription: if the subject required oxygen during hospitalization
Measure: Incidence of oxygen use Time: up to 29 daysDescription: if the subject required oxygen, for how long was it required
Measure: Duration of oxygen use Time: up to 29 daysDescription: if the subject required mechanical ventilation during hospitalization
Measure: Incidence of new mechanical ventilation Time: up to 29 daysDescription: if the subject required mechanical ventilation, for how long was it required
Measure: Duration of mechanical ventilation Time: up to 29 daysDescription: the length of hospitalization required
Measure: Duration of hospitalization Time: up to 29 daysDescription: Mortality rates calculated at day 15, 29, and 60.
Measure: Mortality Time: up to 60 daysDescription: The safety of the intervention will be evaluated during the trial period as compared to the control arm as assessed by the cumulative incidence of Grade 3 and 4 AEs and SAEs using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Paediatric Adverse Events, version 2.1 (July 2017).
Measure: Cumulative Incidence of Grade 3 and 4 Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: up to 30 days after last dose of drug adminstrationDescription: To evaluate the virologic efficacy of lopinavir/ritonavir, hydroxychloroquine, or remdesivir as compared to the control arm as assessed by the percent of subjects with SARS-CoV-2 detectable in OP sample at days 3, 5, 8, 11, 15, and 29
Measure: Time to viral clearance of lopinavir/ritonavir as compared to the control arm Time: up to 29 daysThe investigators aim to evaluate the efficacy of pre-exposure prophylaxis with hydroxychloroquine in healthcare workers with high-risk of SARS-CoV-2 infection.
Description: Confirmed cases of a COVID-19 (defined by symptoms compatible with COVID-19 and/or a positive PCR for SARS-CoV-2) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative PCR for SARS-CoV-2 at day 0.
Measure: Confirmed cases of a COVID-19 Time: Up to 6 months after start of treatmentDescription: SARS-CoV-2 seroconversion in the PrEP group compared to placebo in during 6 months of follow-up in healthcare workers with negative serology at day 0.
Measure: SARS-CoV-2 seroconversion Time: Up to 6 months after start of treatmentDescription: Incidence of clinical and/or laboratory adverse events will be compared in the PrEP group and in the placebo arm.
Measure: Occurrence of any adverse event related with hydroxychloroquine treatment Time: Up to 6 months after start of treatmentDescription: Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers will be estimated by the number of healthcare workers diagnosed with COVID-19 in the placebo group, among the total of healthcare workers included in the non-PrEP group during the study period.
Measure: Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers Time: Up to 6 months after start of treatmentDescription: A repository (biobank) of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection.
Measure: COVID-19 Biobank Time: Up to 6 months after start of treatmentCOVID-19 is a respiratory disease caused by the new coronavirus (SARS-CoV-2) and causes considerable morbidity and mortality. Currently, there is no vaccine or therapeutic agent to prevent and treat a SARS-CoV-2 infection. This clinical trial is designed to evaluate the use of Tocilizumab in combination with hydroxychloroquine and azithromycin for the treatment of hospitalized adult patients with COVID-19.
Convalescent plasma (CP) has been used in recent years as an empirical treatment strategy when there is no vaccine or treatment available for infectious diseases. In the latest viral epidemics, such as the Ebola outbreak in West Africa in 2014, the World Health Organization issued a document outlining a protocol for the use of whole blood or plasma collected from patients who have recovered from the Ebola virus disease by transfusion to empirically treat local infectious outbreaks
Description: Copies of COVID-19 per ml
Measure: Change in Viral Load Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin M COVID-19 antibodies
Measure: Change in Immunoglobulin M COVID-19 Titers Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin G COVID-19 antibodies
Measure: Change in Immunoglobulin G COVID-19 Titers Time: Days 0, 4, 7, 14 and 28Description: Proportion of patients with Intensive Care Unit Admission requirement (days 7, 14 and 28)
Measure: Intensive Care Unit Admission Time: Days 7, 14 and 28Description: Days of Intensive Care Unit management (days 7, 14 and 28)
Measure: Length of Intensive Care Unit stay Time: Days 7, 14 and 28Description: Days of Hospitalization (days 7, 14 and 28)
Measure: Length of hospital stay (days) Time: Days 7, 14 and 28Description: Proportion of patients with mechanical ventilation (days 7, 14 and 28)
Measure: Requirement of mechanical ventilation Time: Days 7, 14 and 28Description: Days with mechanical ventilation (days 7, 14 and 28)
Measure: Duration (days) of mechanical ventilation Time: Days 7, 14 and 28Description: 1. Hospital discharge; 2. Hospitalization, not requiring supplemental oxygen; 3. Hospitalization, requiring supplemental oxygen (but not Noninvasive Ventilation/ HFNC); 4. Intensive care unit/hospitalization, requiring Noninvasive Ventilation/ HFNC therapy; 5. Intensive care unit, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 6. Death. (days 7, 14 and 28)
Measure: Clinical status assessed according to the World Health Organization guideline Time: Days 7, 14 and 28Description: Proportion of death patients at days 7, 14 and 28
Measure: Mortality Time: Days 7, 14 and 28ORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)
Measure: COVID Ordinal Outcomes Scale on Day 15 Time: assessed on study day 15Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 15 Time: assessed on study day 15Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 29 Time: assessed on study day 29Description: We will determine the COVID Ordinal Scale for all patients on study day 3
Measure: COVID Ordinal Outcomes Scale on Study Day 3 Time: assessed on study day 3Description: We will determine the COVID Ordinal Scale on study day 8
Measure: COVID Ordinal Outcomes Scale on Study Day 8 Time: assessed on study day 8Description: We will determine the COVID Ordinal Scale on study day 29
Measure: COVID Ordinal Outcomes Scale on Study Day 29 Time: assessed on study day 29Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28 Time: Enrollment to Day 28Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Measure: Oxygen-free days through Day 28 Time: 28 days after randomizationDescription: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Measure: Ventilator-free days through Day 28 Time: 28 days after randomizationDescription: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Measure: Vasopressor-free days through Day 28 Time: 28 days after randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measure: Hospital-free days to Day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience seizure between randomization and day 28
Measure: Number of patients with seizures to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Measure: Number of patients with atrial or ventricular arrhythmia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience cardiac arrest between randomization and day 28
Measure: Number of patients with cardiac arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Measure: Number of patients with acute pancreatitis arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute kidney injury between randomization and day 28
Measure: Number of patients with acute kidney injury to day28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Measure: Number of patients with receipt of renal replacement therapy to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Measure: Number of patients with symptomatic hypoglycemia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28
Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Measure: Number of patients with severe dermatologic reaction to day 28 Time: 28 days after randomizationIn order to assess the efficacy of hydroxychloroquine treatment weekly for a total of 7 weeks in the prevention of COVID-19 infection, three hundred sixty (360) Healthcare workers with high risk exposure to patients infected with COVID-19 will be tested for COVID-19 infection via nasopharyngeal (NP) swab once weekly for 7 weeks. Of those, one hundred eighty (180) will receive weekly doses of hydroxychloroquine for the duration of the study. Subjects who opt not to receive the study drug will form the control group.
Description: Rate of COVID-19 positive conversion on weekly nasopharyngeal (NP) sampling
Measure: Rate of COVID-19 positive conversion Time: 7 weeksDescription: Time-to-first clinical event consisting of a persistent change for any of the following: One positive NP sample Common clinical symptoms of COVID-19 infection including fever, cough, and shortness of breath Less common signs and symptoms of COVID-19 infection including headache, muscle pain, abdominal pain, sputum production, and sore throat
Measure: Time-to-first clinical event Time: 7 weeksDescription: Time-to-first clinical worsening event consisting of any of the following: Hospitalization for COVID-19 infection Intensive care unit admission for COVID-19 infection All cause death
Measure: Time-to-first clinical worsening event Time: 7 weeksThis study will compare two drugs (hydroxychloroquine and azithromycin) to see if hydroxychloroquine is better than azithromycin in treating outpatients with suspected or confirmed COVID-19.
Description: Admitted to a hospital (not merely kept for emergency room observation)
Measure: Hospitalization within 14 days of enrollment Time: From enrollment to 14 days after enrollmentDescription: Hospital-free days at 28 days (number of days patient not in hospital); calculated as worst-rank ordinal with mortality by day 28 assigned the worst score
Measure: Hospital-free days at 28 days Time: Admission (day 1) to 28 days after admission (day 28)Description: Ventilator-free days at 28 days (number of days patient not on a ventilator); calculated as worst-rank ordinal with mortality by day 28 assigned the worst score
Measure: Ventilator-free days at 28 days Time: Admission (day 1) to 28 days after admission (day 28)Description: ICU-free days at 28 days, calculated as worst-rank ordinal with mortality by day 28 assigned the worst score
Measure: ICU-free days at 28 days Time: Admission (day 1) to 28 days after admission (day 28)This is a Phase II interventional study will test the efficacy of quintuple therapy (Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc) in the treatment of patients with COVID-19 infection).
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using Quintuple Therapy Time: 12 weeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or Progression of Symptomatic Days Time: 12 weeksDescription: Assess the symptom response to study therapy as measured by the survey in the EDC
Measure: Assess the safety of Quintuple Therapy Time: 12 weeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via pulse Time: 12 weeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via oxygen saturation Time: 12 weeksDescription: EKG response from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via EKG Time: 12 weeksDescription: Assess Adverse Events and Serious Adverse Events due to Quintuple Therapy
Measure: Assess Tolerability of Quintuple Therapy Time: 12 weeksHealthcare workers are particularly at risk of SARS-CoV-2. This study aims to assess the efficacy of a daily single dose of tenofovir disoproxil fumarate (TDF) (245 mg)/ Emtricitabine (FTC) (200 mg), a daily single dose of hydroxychloroquine (HC) (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 70 years in public and private hospitals in Spain.
Description: assessed by: No symptoms Mild symptoms: general malaise, fever, cough, myalgia, asthenia. Moderate symptoms: mild symptoms plus shortness of breath, Severe symptoms: mild symptoms plus respiratory insufficiency that requires admission in intensive care unit and mechanical ventilation
Measure: Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19) Time: 12 weeksThis study will assess the efficacy of hydroxychloroquine in reducing the severity of symptoms in patients with COVID-19
Description: This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.
Measure: Total Hospitalization Time: 14 daysDescription: This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.
Measure: Total Mechanical Ventilation Time: 14 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 2 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 5 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 10 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 14 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 2 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 5 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 10 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 14 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 2 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 5 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 10 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 14 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 2 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 5 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 10 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 14 daysDescription: Number of enrolled patients who have died within the specified time frame
Measure: Total mortality Time: 28 daysThis is a Phase II interventional study testing whether treatment with hydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of COVID-19
Description: Any symptoms of COVID-19 will be recorded in a daily diary. Symptoms (including fever measured in degrees Fahrenheit, dry cough, productive cough, difficulty speaking, wheezing, dry mouth, headache, chest tightness, difficulty with exertion, shortness of breath, sore throat, malaise, and diarrhea) will be rated as not present, mild, moderate, or severe.
Measure: Prevention of COVID-19 symptoms as recorded in a daily diary Time: 24 weeksDescription: To assess the presence or absence of side effects (graded 1-5), and whether they are tolerable (grade 1-2). AE and SAE will be recorded.
Measure: Safety as determined by presence or absence of Adverse Events and Serious Adverse Events Time: 24 weeksThis is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: 1. Standard of care alone 2. Standard of care plus hydroxychloroquine 3. Standard of care plus azithromycin 4. Standard of care plus hydroxychloroquine plus azithromycin
Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: World Health Organization (WHO) ordinal scale measured at 14 days after enrollment Time: Day 14Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: WHO ordinal scale measured at 28 days after enrollment Time: Day 28Background: Aim: To demonstrate the efficacy of low-dose hydroxychloroquine as primary prevention in healthcare workers Design, participants and interventions: Prospective, randomized, parallel group, double-blinded, placebo controlled, study. including 440 participants who will be randomised to 2 treatment arms: hydroxychloroquine or placebo. Outcome variables: symptomatic or asymptomatic SARS-CoV-2 infection confirmed by PCR, viral load during SARS-CoV-2 infection, seroconversion during the study period, incidence of any acute respiratory infection, days of sick leave. Statistical considerations: No trials have been published investigating the efficacy of HCQ as primary prophylaxis of SARS-CoV-2 infection in health care workers. Thus, sample size calculations in the proposed trial are based on the investigators' best estimates for several parameters. In accordance to the effect of oseltamivir against symptomatic influenza, we assumed an approximate effectiveness of approximately 60% (HR of 0.4) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464969/) as realistic. As a prophylactic intervention with HCQ, which may have side effects and for which supply shortage can be expected, was judged justifiable only if its effectiveness is high, we based our sample size consideration on a HR of 0.3. To estimate the probability of an event in both the experimental and the control group, very little data is available. In a Dutch point-prevalence study 0-10% of health-care workers were infected depending on the healthcare institution, depending on the hospital. This point-prevalence study was performed between 6 and 9 March, when the reported number of cases in the Netherlands was 33 and 77, respectively, according to the RIVM (https://www.rivm.nl/nieuws/resultaat-steekproef-4-ziekenhuismedewerkers-heeft-coronavirus). Additionally, in an a report published in the Lancet, 20% of responding healthcare workers in Italy were found to be infected with SARS-CoV2 within less than one month (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30627-9/fulltext). Several media reports indicate that this proportion is similar across various healthcare institutions and countries (https://www.nytimes.com/2020/03/24/world/europe/coronavirus-europe-covid-19.html) and (https://www.aljazeera.com/news/2020/03/spain-tightens-restrictions-week-lockdown-begins-2003 30191539568.html). As the proposed study will be performed in a high-risk setting, we assumed an event (i.e. PCR positivity) probability of 10% in the control group and 3% in the experimental arm after the maximum study period. In summary, a sample size of 210 participants per arm is necessary to detect a HR of 0.3 with a power of 80.3% with an alpha-error of 0.05. To account for drop-outs and asymptomatic, undetected infection at inclusion or past infection with existing immunity, an additional 10 participants will randomized per treatment arm. The overall study population is therefore 440 participants. Statistical analysis will be based on two populations: A Modified Intention to Treat population excluding those who withdrew consent after randomization and those with a positive serology at baseline. And a per protocol population including all randomized subjects who completed at least 3 out of 4 follow-up visits and took at least 80% of all doses of study medication.
To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8hr thrice a day for 5 days) vs oseltamivir (75 mg orally twice a day for 5 days) vs Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes).
Description: The laboratory-based primary outcome will be turning test negative for COVID-19 on RT-qPCR calculated as viral load of < 150 i.u
Measure: Laboratory Result Time: Day 07 on follow-upDescription: The clinical primary outcome will be improvement of two points on a seven-category ordinal scale shown below: Not hospitalized, able to resume normal activities Not hospitalized, but unable to resume normal activities Hospitalization, not requiring supplemental oxygen Hospitalization, requiring supplemental oxygen Hospitalization, requiring noninvasive mechanical ventilation Hospitalization, requiring invasive mechanical ventilation Death
Measure: Clinical Outcome Time: Day 07 on follow-upEvaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.
Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial Methods: Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival. Outcomes: Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline. ICU-LOS D28 and D 90 mortality (in hospital) Tertiary (exploratory) outcomes: Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7. Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.
Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.
Measure: Proportion of alive patients free off mechanical ventilation Time: 14 days after enrolmentDescription: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.
Measure: Proportion of patients who avoided the need of mechanical ventilation Time: 14 daysDescription: Length of stay in intensive care unit
Measure: ICU LOS Time: 28 daysDescription: Proportion of patients who died by day 28
Measure: Mortality28 Time: 28 daysDescription: Proportion of patients who died by day 90
Measure: Mortality90 Time: 90 daysThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In-vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine. The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.
To determine the prevalence and the 3-months incidence of SARS-CoV-2 in cancer patients (Part A). To evaluate the Covid-19 disease-specific mortality rate in cancer patients treated by hydroxychloroquine and azithromycin (Part B).
Coronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19) as well as against other treatments.
Description: Percentage of patients COVID-19 positive that required mechanical ventilation
Measure: Mechanical ventilation requirement Time: Since the diagnosis until two weeks afterThe overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering investigational treatments administration to patients enrolled in the CORIMUNO-19 cohort (NCT04324047). Sarilumab+Azithromycin+Hydroxychloroquine, or Sarilumab only will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation. All patients will receive standard of care along with randomized investigational treatments. Outcomes of included patients will be compared between groups as well as with outcomes of patients in the CORIMUNO-19 cohort treated with other immune modulators or standard of care.
Description: Events considered are: need for ventilation (including invasive and non invasive ventilation), transfer to the Intensive Care Unit, death or new do-not-resuscitate (DNR) decision in the absence ventilation and outside ICU.
Measure: Need for ventilation (including invasive and non invasive ventilation), intensive care or death Time: 14 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: Early improvement: OMS progression scale <= 5 Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: OMS progression scale Time: 4, 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: Number of ICU-free days alive
Measure: ICU-free days alive Time: 14, 28 and 90 daysDescription: Number of ventilation(invasive or non invasive)-free days alive
Measure: Ventilation-free days alive Time: 14 and 28 daysDescription: Number of hospital-free days alive
Measure: Hospital-free days alive Time: 14, 28 and 90 daysDescription: Number of oxygen therapy-free days alive
Measure: Oxygen therapy-free days alive Time: 14 and 28 daysDescription: SARS-CoV-2 viral load measurement by rtPCR
Measure: Time to negative viral excretion Time: 90 daysDescription: Immunophenotyping and multiplex cytokines (blood sample)
Measure: Immunophenotyping and multiplex cytokines Time: 8 daysA novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. SARS-CoV-2 causes an acute and potentially lethal respiratory illness, known as COVID-19, that is threatening to overwhelm health care systems due to a dramatic surge in hospitalized and critically ill patients. Patients hospitalized with COVID-19 typically have been symptomatic for 5-7 days prior to admission, indicating that there is a window during which an effective intervention could significantly alter the course of illness, lessen disease spread, and alleviate the stress on hospital resources. There is no known treatment for COVID-19, though in vitro and one poorly controlled study have identified a potential antiviral activity for HCQ. The rationale for this clinical trial is to measure the efficacy and safety of hydroxychloroquine for reducing viral load and shedding in adult outpatients with confirmed COVID-19.
The present study is a randomized clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the three arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.
Description: Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first.
Measure: Time to clinical improvement Time: From date of randomization until 14 days later.Description: If the patient dies, we have reached an outcome.
Measure: Mortality Time: From date of randomization until 14 days later.Description: Pulse-oxymetry
Measure: SpO2 Improvement Time: Days 1, 2, 3, 4, 5, 6, 7 and 14.Description: Incidence of new mechanical ventilation use
Measure: Incidence of new mechanical ventilation use Time: From date of randomization until 14 days later.Description: Duration of hospitalization (days)
Measure: Duration of hospitalization Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days.This study proposes to evaluate clinical outcomes and viral load in COVID-19 infected patients with early moderate and severe disease admitted to the hospital and randomized to one of three arms. Patients will be randomized to supportive care, OR hydroxychloroquine alone, OR hydroxychloroquine and azithromycin.
Description: ordinal outcome of most severe a patient experienced after inpatient admission
Measure: Most severe outcome Time: 5 daysCurrently there are no US Food and Drug Administration (FDA)-approved drugs specifically for the treatment of patients with COVID-19. At present, clinical management includes infection prevention and control measures, as well as supportive care, including supplementary oxygen and mechanical ventilatory support when indicated. An array of drugs approved for other indications as well as several investigational drugs are being studied in several hundred clinical trials that are underway across the globe; however, currently there are no clinical trials available to patients in Arizona. This study will determine if a specific drug cocktail can improve clinical outcomes in patients with confirmed Mild SARS-CoV-2
Description: measured by time (days) required from initiation of treatment to improvement of clinical status from mild to symptom free
Measure: Improvement of clinical status Time: up to 28 daysDescription: the time of normalization of fever as measured by daily temperature ( - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic)
Measure: Time of clinical recovery of fever Time: up to 15 daysDescription: the time of alleviation of cough as measured by self reported visual analog scale (VAS) cough scale. 1=no cough, 2-3=cough sometimes, 4-6=have a cough but can still do things, 7-8=persistent cough, prevents from doing things, 9-10=cough presents a great deal of discomfort
Measure: Time of clinical recovery of cough Time: up to 28 daysDescription: to determine the safety of these therapies in combination
Measure: Safety as determined by changes in QTC intervals measured by ECG Time: up to 15 daysDescription: to assess the presence or absence of side effects and whether they are tolerable
Measure: Safety as determined by presence of side effects Time: up to 15 daysDescription: improvement in Wisconsin Upper Respiratory Symptom Survey (WURSS-44) 0 to 7 scale, with 0 = Do not have, 1 = Very mild, 3 = Mild, 5 = Moderate, 7 = Severe
Measure: Time to improvement Time: up to 28 daysCCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled, multi-stage trial, which aims to assess the safety and efficacy of novel treatment option of moderate-severe COVID-19. Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.
Description: Composite outcome
Measure: All-cause mortality or need of invasive mechanical ventilation Time: 28 daysDescription: Number of participants with adverse events with possible relation to study drug
Measure: Frequency of adverse events Time: 90 daysDescription: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Measure: Frequency of severe adverse events Time: 90 daysDescription: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities
Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status Time: 90 daysDescription: Number of days without mechanical ventilation
Measure: Ventilator-free days Time: 28 daysDescription: Number of days without organ-failure
Measure: Organ failure-free days Time: 28 daysDescription: Number of days in ICU
Measure: Duration of ICU stay Time: 90 daysDescription: Number of deaths by any cause
Measure: Mortality rate Time: 7, 14, 21, 28 and 90 daysDescription: Days from the date of hospital admission for COVID-19 to the date of discharge
Measure: Length of hospital stay Time: 90 daysDescription: Days requiring supplement oxygen
Measure: Duration of supplemental oxygen Time: 90 daysThis study is a randomized, open label clinical trial to evaluate the safety and efficacy of hydroxychloroquine (HCQ) plus usual care compared to usual care in approximately 350 hospitalized patients diagnosed with COVID-19. The study will be a 2-arm, non-blinded comparison between open label hydroxychloroquine and usual care. The course of treatment (HCQ) is five days. Participants will be followed to study day 28.
Description: Clinical Status (on a 7-point ordinal scale) at day 15 Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death
Measure: i. Clinical status Time: Clinical Status (on a 7-point ordinal scale) at day 15Description: Oxygenation free days in the first 28 days Incidence and duration of new oxygen use during the study
Measure: Oxygenation Time: up to day 28Description: Ventilator free days in the first 28 days Incidence and duration of new mechanical ventilation use during hospitalization
Measure: Mechanical Ventilation Time: up to day 28Description: Duration of hospitalization (days)
Measure: Hospitalization Time: up to day 28Description: 28-day mortality
Measure: Mortality Time: up to day 28This is a PILOT STUDY, a Phase III double-blind, randomized, placebo-controlled clinical study in which we assess the clinical effect of the prophylactic administration of hydroxychloroquine vs. placebo to healthcare workers working at our University Hospital (HUN). Participants in each arm (n = 43) will be administered with a unique loading dose of 800 mg of hydroxychloroquine the first day followed by 400 mg/week for 90 days. The population to be studied (uninfected healthcare personnel) will be highly exposed to SARS-CoV-2 infection. An active search should be made for individuals who become infected while participating in the study, hence, once the informed consent form is signed, the molecular test for the diagnosis of SARS-CoV-2 infection by RT-PCR will be carried out every 4 days in order to determine as closely as possible the moment the participant becomes positive. The results of the diagnostic RT-qPCR tests will be confronted with: (i) the results of immune monitoring of at least 30 immunological parameters in leukocytes and in plasma (levels of selected cytokines and chemokines analyzed by automated flow cytometry software and (ii) the daily recording of data for the presence or absence of signs and symptoms associated with SARS-Cov-2 infection. For the recording of immune monitoring 20mL blood samples will be taken at eight-time points throughout the 90 days of the stud.
Description: Number of participants with treatment-related adverse events as associated administration of hydroxychloroquine or placebo.
Measure: Adverse effects Time: six months after administration of hydroxychloroquine or placeboDescription: Percentage of expression of immune senescence in cells of the immune system of individuals highly exposed to COVID-19 who receive hydroxychloroquine prophylactically vs. placebo.
Measure: Immune-score Time: six months after administration of hydroxychloroquine or placeboDescription: Correlate the immunological profile of highly exposed individuals with SARS-CoV-2 with the clinic of COVID-19.
Measure: COVID-19 prevention Time: six months after administration of hydroxychloroquine or placeboDescription: Determine the clinical outcome in observation timeframe of highly exposed personnel when receiving hydroxychloroquine vs. placebo prophylactically.
Measure: Clinical response Time: six months after administration of hydroxychloroquine or placeboStudy of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.
Description: The number of patients with development of respiratory failure requiring transfer to the ICU.
Measure: 1st primary endpoint for group 1 Time: up to 3 monthsDescription: The period of clinical recovery.
Measure: 2nd primary endpoint for group 1 Time: through study completion, an average of 3 monthsDescription: The period of clinical recovery.
Measure: 1st primary endpoint for group 2 Time: through study completion, an average of 3 monthsDescription: Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)
Measure: 2nd primary endpoint for group 2 Time: through study completion, an average of 3 monthsDescription: A change in viral load by conducting PCR assay through different timeframes
Measure: 1st secondary endpoint for group 1 Time: on days 5, 10 and 90Description: Frequency of clinical recovery on day 10 from the start of therapy
Measure: 2nd secondary endpoint for group 1 Time: on day 10Description: The retention time of the reaction temperature from the start of treatment.
Measure: 3d secondary endpoint for group 1 Time: up to 3 monthsDescription: Concentration of C-reactive protein in blood plasma.
Measure: 4th secondary endpoint for group 1 Time: up to 3 monthsDescription: Respiratory index.
Measure: 5th secondary endpoint for group 1 Time: up to 3 monthsDescription: Frequency of adverse events and serious adverse events
Measure: 6th secondary endpoint for group 1 Time: through study completion, an average of 3 monthsDescription: A change in viral load by conducting PCR assay through different timeframes
Measure: 1st secondary endpoint for group 2 Time: on days 5, 10 and 90Description: Respiratory index.
Measure: 2nd secondary endpoint for group 2 Time: up to 3 monthsDescription: The retention time of the reaction temperature from the start of treatment.
Measure: 3d secondary endpoint for group 2 Time: up to 3 monthsDescription: Concentration of C-reactive protein in blood plasma.
Measure: 4th secondary endpoint for group 2 Time: up to 3 monthsDescription: Number of patients required transition to alternative therapy schedule
Measure: 5th secondary endpoint for group 2 Time: through study completion, an average of 3 monthsDescription: Frequency of adverse events and serious adverse events
Measure: 6th secondary endpoint for group 2 Time: through study completion, an average of 3 monthsSince end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia
Description: A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.
Measure: Rate of patients reaching a significant hypoxemia, in each arms. Time: From day 0 to day 7Healthcare workers (HCW) at risk of Covid-19 will have baseline serology for SARS-CoV-2 to see if they are already immune to Covid-19. HCW will get baseline assessment and if meeting inclusion criteria and no exclusion criteria they will be randomized in a 2:1 ratio to hydroxychloroquine or Vitamin C on a weekly basis for three months. Subjects will complete daily diary of symptoms and temperature, and will have repeat SARS-CoV-2 serology at 6 weeks and 3 months to determine seroconversion.
Description: Percentage of healthcare worker who develop antibodies to SARS-CoV-2
Measure: COVID-19 Seroconversion rate Time: 3 monthsDescription: Percentage of study subjects who require admission to a hospital for Covid-19
Measure: Admission for Covid-19 Time: 3 monthsThe purpose of this clinical trial is to assess the safety and efficacy of Clevudine 120 mg once a day for 14 days (maximum up to 21 days) and of Hydroxychloroquine 200mg twice a day for 14 days (maximum up to 21 days) of administration in patients with moderate COVID-19.
Description: The primary efficacy endpoint for this clinical trial is the rate of patients with negative SARS-Coronavirus-2 (SARS-CoV-2) in a two-day continuous Real-Time-RT-PCR test from baseline to before the 15th day.
Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2) Time: within 15daysSingle blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.
Description: Mortality rate evaluated 28 days after randomization
Measure: Day-28 mortality Time: 28 days after randomizationDescription: Ventilator-free days (VFDs) at 28 days are one of several organ failure-free outcome measures to quantify the efficacy of therapies and interventions. VFDs are typically defined as follows: VFDs = 0 if subject dies within 28 days of mechanical ventilation. VFDs = 28 − x if successfully liberated from ventilation x days after initiation. VFDs = 0 if the subject is mechanically ventilated for >28 days.
Measure: Ventilator-free days Time: 28 days after randomizationDescription: Mortality rate evaluated during Intensive care unit stay
Measure: Intensive Care Unit mortality Time: Up to 60 days after randomizationDescription: Mortality rate evaluated 60 days after randomization
Measure: Day-60 mortality Time: 60 days after randomizationDescription: Number of patients with pneumonia diagnosed during intensive care unit stay
Measure: Nosocomial pneumonia Time: Up to 60 days after randomizationDescription: Number of patients with bacteremia diagnosed during intensive care unit
Measure: Bacteremia Time: Up to 60 days after randomizationDescription: Placement of ECMO during intensive care unit stay
Measure: Extra corporeal membrane oxygenation (ECMO) Time: Up to 60days after randomizationDescription: Number of patients who underwent tracheostomy during intensive care unit stay
Measure: Tracheostomy Time: Up to 60 days after randomizationDescription: Number of Prone position session
Measure: Prone Position Time: Up to 60 days after randomizationThe novel coronavirus (SARS-CoV-2), is a single-stranded RNA coronavirus. The virus was first isolated from patients presented with pneumonia in Wuhan in December 2019. Sequences of the Wuhan betacoronavirus show similarities to betacoronaviruses found in bats, sharing a common ancestor with the 2003 SARS coronavirus (SARS-CoV) and the bat coronavirus HKU9, a virus found in fruit bats. Similar to SARS-CoV, it is a member of Beta-CoV lineage B. Five genomes of the novel coronavirus have been initially isolated and reported including BetaCoV/Wuhan/IVDC-HB-01/2019, BetaCoV/Wuhan/IVDC-HB-04/2020, BetaCoV/Wuhan/IVDC-HB-05/2019, BetaCoV/Wuhan/WIV04/2019, and BetaCoV/Wuhan/IPBCAMS-WH-01/2019 from the China CDC. The SARS-CoV-2 has since spread from China to the rest of the world. As of 5 April 2020, more than 1.05 million people been confirmed to have infected by SARS-CoV-2, resulting in more than 500,000 deaths. No specific antiviral treatment for the SARS-CoV-2 is currently available, but existing medication could be repurposed. Genetic sequencing demonstrated similarity of the SARS-CoV-2 to the SARS-CoV and MERS CoV.2 We expect patients infected with the SARS-CoV-2 will also present similarly with initial upper respiratory tract symptoms including fever, cough, sputum, myalgia and shortness or breath. More severe cases might complicate with pneumonia and required ventilatory or ECMO support. According to our previous studies in 2003 on patients hospitalized for severe SARS-CoV, the viral load peaked between day 7 from symptoms onset and coincided with clinical deterioration of pneumonia and respiratory failure, with majority of the patients required intensive care support. Higher viral load isolated from different human system also correlated with worsened SARS manifestation and complications. Previously, we have demonstrated that interferon-beta 1b, commonly used in the treatment of multiple sclerosis and lopinavir/ ritonavir, also demonstrated to improve the outcome of MERS-CoV infection in a non-human primate model of common marmoset. A non-randomized trial has also suggested that a combination of hydroxychloroquine and azithromycin might be effective in suppressing SARS-CoV-2 viral load in patients, despite in-vitro activity was only found in hydroxychloroquine. Therefore, we propose to conduct an open-label randomized controlled trial on a short course of interferon β-1b and hydroxychloroquine combination treatment for patients hospitalized for COVID-19 infection.
Description: Time to negative NPS SARS-CoV-2 viral RT-PCR
Measure: Time to negative NPS viral load Time: 4 weeksDescription: Time to complete allevation of symptoms as defined by NEWS of 0 maintained for 24 hours
Measure: Time to NEWS 0 Time: 4 weeksDescription: Days of hospital stay
Measure: Length of Hospitalisation Time: 4 weeksDescription: Time to negative SARS-CoV-2 viral RT-PCR in all clinical samples
Measure: Time to negative viral load in all clinical samples Time: 4 weeksDescription: Treatment related adverse events
Measure: Adverse events Time: 4 weeksDescription: 30-day mortality
Measure: Mortality Time: 30 daysDescription: Cytokine/ chemokine
Measure: Inflammatory markers changes Time: 4 weeks from diagnosisGiven the high prevalence of COVID19 illness (both SARS-CoV-2 RT-PCR confirmed and highly suspect cases) among healthcare workers (HCW) within the Montefiore Health System (MHS), hydroxychloroquine (HCQ) will be prescribed to healthcare workers who are at the highest risk for severe COVID19 illness.
Description: Time that it takes for symptoms to be resolved in those who were treated vs untreated
Measure: Time to resolution of symptoms Time: up to 4 weeksThis study aims to examine the tolerability of high dose hydroxychloroquine in patients with COVID-19 who are not yet hospitalized, but have risk factors for disease progression and complications.
Description: Number of subjects requiring HCQ dose modifications
Measure: Tolerability of high dose HCQ as measured by HCQ dose modification Time: 14 daysDescription: Number of subjects that discontinue HCQ
Measure: Tolerability of high dose HCQ as measured by discontinuation of HCQ Time: 14 daysDescription: Number of Adverse Events observed in all subjects for the duration of the study
Measure: Tolerability of High Dose HCQ as measured by Adverse Events Time: 14 daysDescription: Number of patients admitted to hospital during study period
Measure: Rate of hospitalization due to COVID-19 as measured by number of patients hospitalized Time: 14 daysDescription: The number of days to reach first fever normalization (criteria for normalization: temperature < 100.4 F)
Measure: Time to defervescence as measured in days while on treatment protocol Time: 14 daysDescription: Number of days to resolve other symptoms, as assessed by a standardized questionnaire for symptom assessment.
Measure: Resolution of other COVID-19 symptoms measured in days while on treatment protocol Time: 14 daysTo test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Measure: Percentage of virus free subjects Time: 7 days after initiation of trialDescription: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Measure: Disease severity Time: 6 daysDescription: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: Number of subjects in each arm who die secondary to Covid-19 infection
Measure: Incidence of Death Time: 70 Days (10 weeks)Description: Number of subjects in each arm who have confirmed Covid-19 infection
Measure: Incidence of confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Number of subjects in each arm who discontinue or withdraw medication use for any reason
Measure: Incidence of all-cause study medication discontinuation or withdrawal Time: 14 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)This trial will estimate the efficacy and tolerance of several experimental treatments to prevent hospitalization or death in outpatients aged 65 years or above with Symptomatic SARS-CoV-2 Infection (COVID-19).
Description: Proportion of participants with an occurrence of death
Measure: Death Time: From inclusion (day0) to day 14Description: Proportion of deaths, overall and by cause, in each group
Measure: Death and causes of death Time: From inclusion (day0) to day 28Description: Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR
Measure: Haematological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Biochemical markers in each group : ferritin, serum creatinine, urea, sodium, potassium, chlorine, calcium, magnesium, albumin, bicarbonates / tCO2, LDH, CPK, ASAT, ALAT, uricemia
Measure: Biochemical markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Inflammatory markers in each group : PCT, CRP
Measure: Inflammatory markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of immunological markers in each group : B ans T Cells phenotypic profiles
Measure: Immunological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse events Time: from inclusion (day 0) to day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse reactions Time: from inclusion (day 0) to day 14Description: Plasma concentration of the study drugs at D7
Measure: Plasma concentration Time: day 7Description: Acceptability of the treatment by participant will be assessed with an interview
Measure: Acceptability of the treatment Time: from inclusion (day 0) to day 10Introduction: The COVID-19 pandemic is characterized by significant morbidity and mortality. It is caused by a novel coronavirus with no current specific prevention nor treatment therapies. Treatments have been administered to patients with COVID-19 in order to control viral infection, among them: Chloroquine (CQ) and Hydroxychloroquine (HCQ), Lopinavir/Ritonavir (Lop/r), Remdesivir, Favipavir, acting over bacterial co-infection Azithromycin (Azithro), or modifying the inflammatory response of the host (Tocilizumab). Clinical trials offer conflicting evidence regarding the effectiveness and safety of therapies The real effectiveness and safety profile of the treatments for COVID-19 remains unknown. Objective: Evaluate the effectiveness and safety of pharmacological therapies used to treat adult patients with COVID-19. Methods: Pragmatic randomized controlled trial. Study population: Adults aged 18 years or over with a positive real-time polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome CoV-2 (SARS CoV-2) and diagnosis of mild, severe or critical pneumonia, requiring hospital management at six hospitals in Colombia. Exclusion criteria: Pregnancy, known allergy to treatment, cirrhosis or hepatic abnormality (transaminases greater than 5 reference values), prolonged QT interval, glomerular filtration rate lesser than 30 ml/min/1.73m^2, history of lung fibrosis, advanced or metastatic cancer. Sample size: 1,600 participants. The study will be carried out in two phases. The first phase will be conducted with 480 participants and aims to identify treatments with higher or minimum potential, discontinue treatments with higher toxicity and have opportunity of introducing new treatments with potential efficacy. The second phase will be conducted with 1,120 participants to evaluate the effectiveness of the selected treatments. Four interventions have been defined: I1 HCQ, I2 HCQ plus Lop/r, I3 HCQ plus Azithro and I4 standard treatment. Within each institution, participants will be randomly assigned to one of the treatment arms assigned to that institution. Concealment will be kept through a central telephone. Treatment administration will be open. Variables: Sociodemographic and clinical at recruitment; (comorbidities, need for therapeutic support , grade of invasion at admission). Primary outcomes. Effectiveness: Mortality. Safety: Serious adverse events (AE) assessed by the NCI Community Oncology Research Program (NCORP) Guidance for Collection of Adverse Events Related to COVID-19 Infection. Secondary outcomes: Intensive care unit (ICU) admission, requirement of respiratory support, time to death, number of participants cured, any adverse event related to treatment. Analysis: Descriptive for the presentation of summary measures of the basal conditions by type of variable. Bivariate. Description of the basal conditions (with organic failure at admission, without failure at admission), by type of treatment, by participating institution. Description of crude effectiveness and safety by means of the difference of accumulated incidences, each one with 95% confidence intervals (95% CI) Intention to treat analyisis will be done. Adjusted analysis: The ratio and difference of cumulative incidences of mortality at 7 and 28 days and severe adverse events between treatments will be estimated, adjusting for confounding variables using logistic regression models with mixed effects considering each institution as a level or from equations. generalized estimation (GEE). Ethical considerations: The study has a risk beyond minimum according to the Resolution 8430/1993 of the Colombian Ministry of Health. Informed consent will be explained and signed if the patient is in condition to do so. This protocol will undergo evaluation by the ethics committee at each of the participating institutions and at the National University of Colombia. The protocol follows the Helsinki Declaration and institutional protocols for clinical investigation.
Description: Cumulative incidence
Measure: Mortality Time: Post-intervention at day 28Description: Number of participants that develop severe adverse events related to the treatment
Measure: Number of Participants with Treatment Related Severe Adverse Events as Assessed by the NCORP Guidance for Collection of Adverse Events Related to COVID-19 Infection Time: Post-intervention at day 28Description: Cumulative incidence
Measure: Mortality Time: Post-intervention at day 7Description: Number of participants that develop severe adverse events related to the treatment
Measure: Number of Participants with Treatment Related Severe Adverse Events as Assessed by the NCORP Guidance for Collection of Adverse Events Related to COVID-19 Infection Time: Post-intervention at day 7Description: Time from the date of assignment until the date of death from any cause
Measure: Time to death Time: Assessed up to 28 days postinterventionDescription: Number of Participants that require management in the ICU
Measure: Number of Participants that are transferred to the Intensive Care Unit (ICU) Time: Post-intervention at day 28Description: Participants requiring invasive mechanical ventilation
Measure: Number of Participants that need Mechanical Ventilation Support with endotracheal intubation. Time: Up to 28 days after hospital admissionDescription: Number of participants cured assessed RT-PCR for SARS CoV-2, without clinical symptoms and no radiological signs assessed by chest X ray
Measure: Number of participants Cured assessed by Nasopharyngeal swab, oropharyngeal swab, and blood aspiration for COVID19 (RT-PCR) without clinical symptoms and normal chest X ray Time: Up to 28 days after hospital admissionDescription: Any adverse event
Measure: Number of Participants with Any Adverse Event Related to Treatment Assessed by the NCORP Guidance for Collection of Adverse Events Related to COVID-19 Infection Time: Up to 28 days after hospital admissionDescription: Interim assessment of safety, which will be conducted after 480 participants are recruited. It will be evaluated through absolute frequency of severe AE and relative frequency measurements (proportion of total number of participants with severe adverse events divided by the total number of participants treated). It aims to aid the decision of excluding an active treatment arm should that arm have more than 3 serious adverse events in the first 30 participants or a serious adverse events incidence of 10 percent or higher.
Measure: Severe Adverse events Time: Up to 28 days after hospital admissionDescription: Interim assessment of minimum effectiveness, which will be conducted after 480 participants are recruited. It will be evaluated through relative frequency measurements (mortality proportion at 28 days of treatment). It aims to aid the decision of excluding an active treatment arm should that treatment arm have an efficacy lower than 0.2, calculated through futility analysis that assumes an expected difference of 10 percent at the end of the first phase of the study. For all the tests carried out in the interim analysis, the correction of the type I error will be made using the O'Brien-Fleming method.
Measure: Mortality Time: Up to 28 days after hospital admissionThe present study is a randomized, double-blind, controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Shahid Modarres Medical Education Center and Hospital in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.
Description: Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first.
Measure: Time to clinical improvement Time: From date of randomization until 14 days later.Description: If the patient dies, we have reached an outcome.
Measure: Mortality Time: From date of randomization until 14 days later.Description: Pulse-oxymetry
Measure: SpO2 Improvement Time: Days 1, 2, 3, 4, 5, 6, 7 and 14.Description: Incidence of new mechanical ventilation use (Rate)
Measure: Incidence of new mechanical ventilation use Time: From date of randomization until 14 days later.Description: Duration of hospitalization (Days)
Measure: Duration of hospitalization Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days.Description: With incidence of any serious adverse effects, the outcome has happened.
Measure: Cumulative incidence of serious adverse events Time: Days 1, 2, 3, 4, 5, 6, 7 and 14.The present study is a randomized, double-blind, controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Shahid Modarres Medical Education Center and Hospital in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.
Description: Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first.
Measure: Time to clinical improvement Time: From date of randomization until 14 days later.Description: If the patient dies, we have reached an outcome.
Measure: Mortality Time: From date of randomization until 14 days later.Description: Pulse-oxymetry
Measure: oxygen saturation by pulse oximetry (SpO2) Improvement Time: Days 1, 2, 3, 4, 5, 6, 7 and 14.Description: Incidence of new mechanical ventilation use
Measure: Incidence of new mechanical ventilation use Time: From date of randomization until 14 days later.Description: Duration of hospitalization (days)
Measure: Duration of hospitalization Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days.Description: With incidence of any serious adverse effects, the outcome has happened.
Measure: Cumulative incidence of serious adverse events Time: Days 1, 2, 3, 4, 5, 6, 7 and 14.In November 2019, Wuhan city in China, became the center of an outbreak of pneumonia due to a novel coronavirus SARS-CoV-2, which disease was named coronavirus disease 2019 (COVID19) in February, 2020. The COVID19 is much more dangerous for people over 60 with a death rate of 3.6% after 60, 8.0% after 70 and 14.8% after 80 -and according to our Italian colleagues over 20% after 90- against 2.3% in the general population. The elderly patients who died most often had multiple comorbidities and in particular: cardiovascular disease (10.5% mortality), diabetes (7.3%), chronic respiratory disease (6.3%) and hypertension (6%). These elderly patients with COVID19 are therefore very fragile and require treatment that fights the virus but is also adapted to their state of health and age. Most of current therapeutic trials worldwide exclude people aged over 75 years, which is precisely the age group affected by COVID19. We therefore propose to carry out a therapeutic trial specific to the elderly with drugs at doses that are bearable for these patients. Using the WHO, clinicaltrial, pubmed and the Chinese CCDC/CHCTR websites to find the better drugs adapted to elderly people, we decided after concertation between infectiologists and geriatricians to do a four arms clinical trial during two weeks twice a day: Hydroxychloroquine 200mg, Telmisartan 40mg, Azithromycin 250mg and standard care. We therefore hypothesize that one or more of these treatments may have a beneficial effect in controlling COVID19, without major and repeated side effects in elderly patients.
Rationale: Currently there are no approved treatments for COVID-19. In the Dutch treatment protocol guideline (SWAB) designated treatment is supportive care with the option to add chloroquine base (CQ) or hydroxychloroquine (HCQ). CQ and HCQ are implemented because of their in vitro activity, results from small animal studies, and anecdotal patient's data. There are no published randomized studies with these medications in patients with disease caused by any coronavirus. Objective: To evaluate if treatment with only supportive care or addition of one of two anti-COVID_19 agents (chloroquine or hydroxychloroquine) results in less disease progression in patients with moderate to severe COVID-19 who require hospital admission. Study design: Multicentre, cluster randomized cross-over, open label trial. Hospitals will be randomly allocated to one of 3 treatment arms in sequential periods of one week: chloroquine base versus hydroxychloroquine versus supportive care without any drug presumed active against SARS-COV-2. Patients will be treated based on the date of inclusion. Study population: Adults aged of 18 years and older with moderate to severe, with a NEWS-2 score ≤ 5, laboratory confirmed COVID-19, who require hospital admission in a ward outside the Medium Care or Intensive Care. Intervention (if applicable): Depending on the treatment arm, the study subject will receive only supportive care or an addition with one of the two agents active against SARS-CoV-2 (chloroquine or hydroxychloroquine). Main study parameters/endpoints: Disease progression defined as a NEWS-2 score ≥ 7 within 14 days, or admission to Medium Care or Intensive Care Unit, or death.
Description: Composite endpoint with disease progression defined as a NEWS2score ≥ 7 within 14 days or resulting in admission to Intensive/Medium Care unit or resulting in death within 14 days.
Measure: Composite endpoint with disease progression defined as a NEWS2score ≥ 7 within 14 days or resulting in admission to Intensive/Medium Care unit or resulting in death within 14 days. Time: 14 daysDescription: Secondary study parameters/endpoints Side effects of different drugs leading to regimen change or discontinuation of the antiviral treatment
Measure: Side effects Time: 28 daysWe propose a 3-arm RCT to determine the efficacy of hydroxychloroquine or azithromycin in treating mild to moderate COVID-19 among Veterans in the outpatient setting.
This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksDescription: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeksThis is a Italian, superiority, open label cluster-randomised, interventional clinical trial aimed at assessing whether the treatment with Hydroxychloroquine can reduce the percentage of symptomatic subjects compared to observation only in household members/contacts of COVID-19 patients (Group 1) and if the treatment with Hydroxychloroquine could be introduced in early phase COVID-19 population (Group 2). The participants will be randomised to receive either: Arm A) hydroxychloroquine vs Arm B) Observation (2:1 randomisation).
Description: Group 1:The primary endpoint/outcome measure is the proportion of subjects of Group 1 who become symptomatic and/or swab positive in each arm within 1 month from randomization.
Measure: the proportion of subjects of Group 1 who become symptomatic and/or swab positive in each arm within 1 month from randomization. Time: within 1 month from randomizationDescription: Group 2: The primary endpoint/outcome measure is the proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization.
Measure: the proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization. Time: within 14 days from randomizationDescription: The proportion of subjects with positive swabs in randomized population of SARS-CoV-2-exposed subjects ( Group 1) within 1 month from randomization in both arms
Measure: The proportion of subjects with positive swabs in Group 1 within 1 month from randomization in both arms Time: within 1 month from randomizationDescription: The proportion of subjects of Group 1 who become symptomatic in each arm within 1 month from randomization, in subgroup population identified by stratification factors, class of age and gender.
Measure: The proportion of subjects of Group 1 who become symptomatic in each arm within 1 month from randomization Time: within 1 month from randomizationDescription: The proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization, in subgroup population identified by stratification factors, class of age and gender.
Measure: The proportion of subjects of Group 2 who become swab negative in each arm within 14 days from randomization. Time: within 14 days from randomizationDescription: The proportion of subjects of Group 2 who become swab negative in each arm within 1 month from randomization in overall population and in subgroup population identified by stratification factors, class of age and gender.
Measure: The proportion of subjects of Group 2 who become swab negative in each arm within 1 month from randomization in overall population and in subgroup population Time: within 1 month from randomizationDescription: Absolute and relative frequencies of Serious Adverse Events (CTCAE version 5.0) in both arms for the Group 1 and Group 2.
Measure: Absolute and relative frequencies of Serious Adverse Events Time: up to 10 monthsDescription: Variation in Quality of Life scores EQ-5D-5L (EQ-5D descriptive system with 5 severity levels from better to worse, and the EQ visual analogue scale (EQ VAS, scale from 100 to 0, high is better) in different time points (weekly) respect to baseline values in both Group 1 and Group 2 populations.
Measure: Variation in Quality of Life scores in different time points Time: up to 10 monthsThis is a prospective, randomized, participant-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.
Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine
Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale Time: Day 5Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine
Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5 Time: Day 0 to Day 28 and at Day 5Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)
Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events Time: Day 0 to Day 28Description: Assess length of hospitalization
Measure: Duration of Initial Hospitalization Time: Day 0 to Day 28Description: Assess number of deaths during study follow-up
Measure: Mortality During Follow-Up Time: Day 0 to Day 28Description: Assess number of deaths in the hospital during initial hospitalization
Measure: Mortality During Initial Hospitalization Time: Day 0 to Day 28Description: Assessing utilization of hospital resources
Measure: Incidence of New Hospital Resource Utilization Time: Day 0 to Day 28Description: Assessing duration of hospital resource utilization
Measure: Duration of Hospital Resource Utilization Time: Day 0 to Day 28Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine
Measure: Changes in Cytokine Profile Time: Day 0 to Day 28COVID-19 is a respiratory disease due to a novel coronavirus (SARS-CoV-2) that causes substantial morbidity and mortality. To date, no treatment has been proved to be effective in COVID-19. Elderly patients and patients with comorbidities have the worse prognosis with a higher risk of hospitalization, ICU admission and death. The efficacy of an early outpatient treatment could be suggested but need to be confirmed. This confirmation is mandatory to improve prognosis of COVID-19 but also to avoid unsuspected deleterious effect of drugs already used in clinical practice but not based on evidence.
Description: Hospitalization at D20
Measure: Hospital admission Time: Day 20Description: This outcome corresponds to the number of patients who died on day 20.
Measure: Effect of treatment on Death at D20 Time: Day 20Description: This outcome corresponds to the number of patients who died on day 60.
Measure: Effect of treatment on Death at D60 Time: Day 60Description: This outcome corresponds to the number of patients who died due to COVID on day 20.
Measure: Effect of treatment on Death due to COVID at D20 Time: Day 20Description: This outcome corresponds to the number of patients who died due to COVID on day 60.
Measure: Effect of treatment on Death due to COVID at D60 Time: Day 60Description: This outcome corresponds to the number of participants who need ICU stay at day 20.
Measure: Effect of treatment on need for ICU stay at D20 Time: Day 20Description: This outcome corresponds to the number of participants who need ICU stay at day 60.
Measure: Effect of treatment on need for ICU stay at D60 Time: Day 60Description: This outcome evaluates the duration of patient's ICU stay at day 20.
Measure: Effect of treatment on duration of ICU stay at D20 Time: Day 20Description: This outcome evaluates the duration of patient's ICU stay at day 60.
Measure: Effect of treatment on duration of ICU stay at D60 Time: Day 60Description: This outcome corresponds to the number of participants who need mechanical ventilation at D20.
Measure: Effect of treatment on need of mechanical ventilation at D20 Time: Day 20Description: This outcome corresponds to the number of participants who need mechanical ventilation at D60.
Measure: Effect of treatment on need of mechanical ventilation at D60 Time: Day 60Description: This outcome corresponds to the duration of patient's mechanical ventilation at D20.
Measure: Effect of treatment on duration of mechanical ventilation at D20 Time: Day 20Description: This outcome corresponds to the duration of patient's mechanical ventilation at D60.
Measure: Effect of treatment on duration of mechanical ventilation at D60 Time: Day 60Description: This outcome evaluates the delay between inclusion and hospitalization at D20.
Measure: Effect of treatment on time to hospitalization at D20 Time: Day 20Description: This outcome evaluates the delay between inclusion and hospitalization at D60.
Measure: Effect of treatment on time to hospitalization at D60 Time: Day 60Description: This outcome evaluates the duration of patient's Hospital stay at D20.
Measure: Effect of treatment on Duration of Hospital stay et D20 Time: Day 20Description: This outcome evaluates the duration of patient's Hospital stay at D60.
Measure: Effect of treatment on Duration of Hospital stay et D60 Time: Day 60Description: This outcome evaluates the duration of symptoms at D20 after treatment.
Measure: Effect of treatment on Duration of symptoms at D20 Time: Day 20Description: This outcome evaluates the duration of symptoms at D60 after treatment.
Measure: Effect of treatment on Duration of symptoms at D60 Time: Day 60Description: This outcome measures the number of participants with treatment-related adverse events as assessed by CTCAE v4.0, at the end of study.
Measure: Incidence of Treatment-Emergent Adverse Events Time: Month 6Description: This outcome evaluates the chest radiological features on Chest HRCT, at 6 months, after treatment.
Measure: Effect of treatment on chest radiological features Time: Month 6Description: This outcome evaluates the Pulmonary function test at 6 month, after treatment.
Measure: Effect of treatment on respiratory capacity Time: Month 6Description: This ouctome eavaluates costs and consequences which will be presented for each stakeholder in a disaggregated way at the end of study.
Measure: Cost consequence analysis Time: Month 6Healthcare personnel are at an increased risk of exposure to SARS-CoV-2 infection while handling such patients. Currently, there is no treatment available for SARS-CoV-2 and stringent preventive measures are advised to avoid or minimize risk of exposure to healthcare workers. There are in vitro studies available which show inhibition of corona virus by hydroxychloroquine, a widely-used agent against malaria and certain autoimmune conditions and of low-cost and limited toxicity. However, evidence regarding its effects in patients is limited. We plan to conduct a randomized controlled trial to evaluate the safety and potential prophylactic efficacy of hydroxychloroquine in preventing secondary SARS-CoV-2 infection among healthcare workers at high-risk of exposure while managing such patients.
Description: Negative RT-PCR for SARS-CoV-2 both at baseline and at end of 12 weeks in experimental arm
Measure: Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period Time: From date of randomization until study completion 12 weeks after treatment initiationDescription: To assess the presence or absence of side effects from HCQ treatment.
Measure: Safety as determined by presence or absence of any adverse event related with hydroxychloroquine treatment Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Symptomatic infection by SARS-CoV-2 defined as cough, dyspnea, fever, myalgia, arthralgia or rhinorrhea.
Measure: Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Disease severity including i) asymptomatic. ii) Mild symptoms but ambulatory. iii) Moderate symptoms requiring hospitalisation. iv) severe symptoms requiring ICU care and oxygen. v) Severe symptoms requiring assisted mechanical ventilation. vi) Death.
Measure: Clinical disease severity in confirmed SARS-CoV-2 participants Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Symptomatic non-COVID viral infection (any other acute respiratory illness with fever but without evidence of epidemiological risk factors such as close contact with SARS-CoV-2 positive patient or travel to or residence in high-risk area).
Measure: Incidence of any acute respiratory infection Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationThis is a randomized, open-label trial to assess the safety and efficacy of hydroxychloroquine, and zinc in combination with either azithromycin or doxycycline in a higher risk COVID-19 positive outpatient population.
Description: Patients will be assessed on day 5 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial)
Measure: Time to Resolution of Symptoms relative to baseline (day 1 of trial) Time: Day 5Description: Patients will be assessed on day 14 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial)
Measure: Time to Resolution of Symptoms relative to baseline (day 1 of trial) Time: Day 14Description: Patients will be assessed on day 21 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial)
Measure: Time to Resolution of Symptoms relative to baseline (day 1 of trial) Time: Day 21Description: Number of participants hospitalized and/or requiring repeat ER visits related to COVID-19 complications
Measure: Number of participants hospitalized and/or requiring repeat ER visits Time: 21 daysDescription: If hospitalized, number of participants admitted to the ICU, and number of days in the ICU
Measure: ICU Length of Stay Time: Until Discharged up to 30 daysDescription: If placed on ventilator, number of days on a ventilator
Measure: Ventilator Time: Until extubated up to 30 daysDescription: Severity of symptoms evaluated at day 5, day 14, and day 21 scored by the participant for feverishness, sore throat, cough, shortness of breath, myalgias. (0 =none; 1 = mild; 2 = moderate; 3 = severe)
Measure: Severity of symptoms Time: Day 5, Day 14, and Day 21Description: Number of participants with adverse events due to drug regimen
Measure: Number of participants with adverse events due to drug regimen Time: 21 daysDescription: Assess all patients to evaluate for QTc prolongation >500ms
Measure: Number of participants with QTc prolongation >500ms Time: Days 1 thru 5, Day 10, Day 21No optimal antiviral intervention has been yet validated to treat COVID-19 disease. Comorbidities, such as older age, obesity, diabetes, history of cardiovascular diseases are associated with poor prognosis. This study aims to evaluate the efficacy of two experimental antiviral treatments, compared to standard of care (SOC), to prevent clinical worsening, hospitalization or death at day 14 in adults with documented SARS-CoV-2 infection, asymptomatic or with symptoms lasting less than 8 days, and associated comorbidities without any severity criteria of the disease at inclusion. Participants will be randomized to receive SOC alone or SOC + hydroxychloroquine 200 mg three times a day during 10 days or SOC + association of niclosamide 2 g at J1 then 500 mg two times a day with diltiazem 60 mg three times a day during 10 days. Efficacy and tolerance of each treatments will be compared across the three treatment groups during the 28 days of follow-up.
Description: Composite criteria
Measure: death Time: At day 14Description: clinical worsening defined by at least one of the NEWS score item > 2 (temperature >39,1°C or<35°C, cardiac rate >111 or ≤40 bpm, respiratory rate > 21 or ≤8 cycles par minute, SaO2 ≤ 93% room air (if its measure is available),need of oxygen
Measure: clinical worsening (composite criteria) Time: At day 14Description: clinical state as reflected by NEWS scoring, the clinical state of the patient regarding respiratory state as defined by the NEWS scoring system
Measure: National Early Warning Score (NEWS) Time: at day 3, day 8, day 14 day 28Description: Number of patients death
Measure: Mortality Time: at day 14 and at day 28Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial
Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15 Time: Day 15Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity
Measure: Modified COVID Ordinal Outcome Scale: Study Day 8 Time: Day 8Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale
Measure: Modified COVID Ordinal Outcome Scale: Study Day 29 Time: Day 29Description: Proportion hospitalized
Measure: Proportion of patients hospitalized: Day 1 to 29 Time: Day 1 to Day 29Description: Number of days from enrollment to hospitalization
Measure: Time to hospitalization Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days from enrollment to resolution of COVID-19 symptoms
Measure: Time to symptom resolution: Day 1 to Day 29 Time: Day 1 to Day 29Description: Survival status
Measure: All-cause, all-location mortality: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of Days without oxygen
Measure: Oxygen-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without fever
Measure: Fever-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without ventilator use
Measure: Ventilator-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the ICU
Measure: ICU-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the hospital
Measure: Hospital-free days: Day 1 to Day 29 Time: Day 1 to Day 29This phase II trial studies the effect of baricitinib in combination with antiviral therapy for the treatment of patients with moderate or severe coronavirus disease-2019 (COVID-19). Treatment with antiviral medications such as hydroxychloroquine, lopinavir/ritonavir, and/or remdesivir may act against infection caused by the virus responsible for COVID-19. Baricitinib may reduce lung inflammation. Giving baricitinib in combination with antiviral therapy may reduce the risk of the disease from getting worse and may help prevent the need for being placed on a ventilator should the disease worsen compared to antiviral therapy alone.
Description: Descriptive statistics, including means, standard deviations, and ranges for continuous variables, as well as percentages and frequencies for categorical variables, will be provided to describe all the clinical findings in a cohort of symptomatic coronavirus disease 2019 (COVID-19)-infected subjects. The collected data will also be graphically presented in boxplots, histograms, and scatter plots. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity, will be made. Group comparisons will be made using either the parametric tests such as t-test and analysis of variance (ANOVA), or the non-parametric statistical method such as Wilcoxon and Kruskal-Wallis tests for continuous variable and Chi-square test for categorical variables. Point estimates, along with the corresponding p-values and 95% confidence intervals will be reported.
Measure: Proportion of patients requiring invasive mechanical ventilation or dying Time: Up to 14 daysDescription: Body temperature will be measured in degrees Fahrenheit using an automated thermometer.
Measure: Identification of clinical features (vitals signs - body temperature) Time: Up to 28 daysDescription: Respiratory rate in times/minute
Measure: Identification of clinical features (vital signs - respiratory rate) Time: Up to 28 daysDescription: Heart rate in beats/minute
Measure: Identification of clinical features (vital signs - heart rate) Time: Up to 28 daysDescription: Blood pressure in mmHg
Measure: Identification of clinical features (vital signs - blood pressure) Time: Up to 28 daysDescription: Chest X-ray or pulmonary computed tomography (CT) will be performed
Measure: Identification of clinical features (Imaging) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - White Blood Count) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Absolute Lymphocyte Count) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Hemoglobin) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Creatinine) Time: Up to 28 daysDescription: CRP is assessed by routinely used determination of CRP.
Measure: Identification of biomarkers (C-reactive protein) Time: Up to 14 daysDescription: IL-6 levels will be assessed using commercial ELISA method
Measure: Identification of biomarkers (Interleukin-6) Time: Up to 14 daysDescription: Tumor Necrosis Factor-alpha as measured in hospital laboratory
Measure: Identification of biomarkers (Tumor Necrosis Factor-alpha) Time: Up to 14 daysDescription: Descriptive statistics, including means, standard deviations, and ranges for continuous variables, as well as percentages and frequencies for categorical variables, will be provided to describe all the clinical findings in a cohort of symptomatic COVID-19-infected subjects. The collected data will also be graphically presented in boxplots, histograms, and scatter plots. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity, will be made. Group comparisons will be made using either the parametric tests such as t-test and ANOVA, or the non-parametric statistical method such as Wilcoxon and Kruskal-Wallis tests for continuous variable and Chi-square test for categorical variables. Point estimates, along with the corresponding p-values and 95% confidence intervals will be reported.
Measure: Identification of adverse events Time: Up to 14 daysCurrently we do not know how best to treat patients infected with COVID-19. This study is looking at whether randomising participants to either a combination of azithromycin, hydroxychloroquine and zinc or favipiravir, alongside usual care, can help patients with suspected or proven COVID-19 infection.
Description: Time from randomisation to clinical improvement by two points on a seven-category ordinal scale: Not hospitalised with resumption of normal activities Not hospitalised, but unable to resume normal Hospitalised, not requiring supplemental oxygen Hospitalised, requiring supplemental oxygen Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both Death
Measure: Time to improvement by two points on a seven-category ordinal scale Time: Up to 28 days from randomisationDescription: Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
Measure: Clinical status on a seven-category ordinal scale (Day 7) Time: Day 7 from randomisationDescription: Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
Measure: Clinical status on a seven-category ordinal scale (Day 14) Time: Day 14 from randomisationDescription: Survival of patients to end of study
Measure: Overall survival Time: 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS score of patient condition, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS score Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for temperature, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for temperature Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for heartrate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for heartrate Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for respiratory rate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for respiratory rate Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for oxygen saturation, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for oxygen saturation. Time: Up to 28 days from randomisationDescription: Frequency of admission of patients to intensive care
Measure: Admission to intensive care Time: Up to 28 days from randomisationDescription: Frequency of requirement to administer mechanical ventilation to patients
Measure: Requirement for mechanical ventilation Time: Up to 28 days from randomisationDescription: Frequency of requirement to administer non-invasive ventilation, continuous positive airways pressure or high-flow oxygen to patients
Measure: Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen Time: Up to 28 days from randomisationDescription: Frequency of culture-confirmed bacterial or fungal infection in patients
Measure: Incidence of bacterial or fungal infection Time: Up to 28 days from randomisationDescription: Frequency and severity of adverse events in patients not directly attributed by clinicians to COVID-19 infection.
Measure: Incidence of adverse events not directly caused by COVID-19 infection. Time: Up to 28 days from randomisation.Description: Frequency of readmission to inpatient care of patients discharged from hospital.
Measure: Readmission to inpatient care Time: Up to 28 days from randomisationThis is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus, through alternative mechanisms to hydroxychloroquine, will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.
Description: Proportion of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.
Measure: Clinical Deterioration Time: 14 daysDescription: The change in (clearance of) viral RNA will be measured by PCR testing at days 1, 14, 28, and 40 days.
Measure: Change in Viral Load Time: 40 daysDescription: Percentage of patients that experience severe respiratory or other organ failure.
Measure: Rate of Organ Failure Time: 28 daysDescription: Percentage of patients requiring ICU admission or ventilation.
Measure: Progression to ICU Care or Ventilation Time: 28 daysDescription: Clinical status will be assessed using the COVID 7-Point Ordinal Outcomes Scale. This scale ranges from 1-7. Lower scores indicate worse outcomes; higher scores indicate fewer symptoms and better outcomes.
Measure: Change in Clinical Status Time: 14 daysDescription: Percentage of patients who have died by day 14.
Measure: Mortality Time: 14 daysDescription: Percentage of patients experiencing severe adverse events, defined as grade 3 non-hematologic or greater by DMID Toxicity Scale for Determining Severity of Adverse Events.
Measure: Rate of severe adverse events Time: 14 daysDescription: Number of days patients do not require oxygen supplementation.
Measure: Oxygen-free days Time: 28 daysDescription: Number of days patients do not require mechanical ventilation.
Measure: Ventilator-free days Time: 28 daysDescription: Number of days patients do not require vasopressor treatment.
Measure: Vasopressor-free days Time: 28 daysDescription: Number of days patients do not require ICU services.
Measure: ICU-free days Time: 28 daysDescription: Number of days patients do not require hospitalization.
Measure: Hospital-free days Time: 28 daysDescription: Proportion of patients meeting Hy's law criteria.
Measure: Patients meeting Hy's Law criteria Time: 28 daysDescription: Proportion of patients with changes in the following liver function tests: Any ALT or AST ≥ 5 x ULN; any AST or ALT ≥ 3 x ULN together with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (eosinophil percent or count above the ULN); Persistent ALT ≥ 3 x ULN for a period of more than 4 weeks
Measure: Liver Function Time: 28 daysDescription: Proportion of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes, or abnormalities including severe QTc prolongation of > 500 ms.
Measure: Heart Function Time: 28 daysOn 11 March 2020, the World Health Organization declared SARS-CoV-2 (commonly called COVID-19) a global pandemic. As in any pandemic, maintaining the health and safety of the healthcare workforce is of great importance as health care workers (HCW) remain a critical line of defence against the spread of COVID-19 and play a vital role in the recovery of those already infected. Frontline HCW, such as those in the emergency department (ED), are at high risk of contracting COVID-19 due to their close proximity to patients who may have the virus. The impact of frontline HCW becoming ill and thus unable to go to work is equally high, and of grave risk to the function of the healthcare system and the ability to minimize the impact of the current pandemic. This study aims to evaluate whether hydroxychloroquine (HCQ), a well-tolerated drug typically used in the prevention of malaria transmission and rheumatic disease, taken before and during exposure to patients with COVID-19, is effective at reducing COVID-19 infections among ED health care workers.
Description: This is a composite endpoint which includes any positive result from a validated SARS-CoV-2 diagnostic assay including detection of viral RNA, or seroconversion by day 104 (14 days after end of the randomization period).
Measure: Microbiologically confirmed COVID-19 (SARS-CoV-2 infection) Time: Samples collected at day 0, 30, 60, 90 and 120Description: Assessed using the DAIDS Table for Grading the Severity of Adverse Events
Measure: Adverse events Time: Assessed at day 30, 60, 90, and day 120Description: Collected weekly from participants via self-report, sent by email
Measure: Symptom duration of COVID-19 Time: Collected every 7 days from day 7 to day 120Description: The number of days (or partial days) spent admitted to an acute care hospital during the study period
Measure: Days of hospitalization attributable to COVID-19 Time: Collected every 7 days from day 7 to day 120Description: the number of days (or partial days) requiring i) non-invasive and ii) endotracheal intubation with ventilation during the study period
Measure: Respiratory failure requiring ventilatory support attributable to COVID-19 Time: Collected every 7 days from day 7 to day 120Description: Mortality attributable to COVID-19 and all-cause mortality during the study period
Measure: Mortality Time: Collected every 7 days from day 7 to day 120Description: Number of days ineligible/unable to work due to COVID-19
Measure: Impact on work eligibility Time: Collected every 7 days from day 7 to day 120Description: COVID-19 reactive serology
Measure: Seropositivity Time: Blood collected at day 0, 30, 60, 90, 120Description: Short-term psychological impact of exposure to COVID-19 measured using the K10, a validated measure of non-specific psychological distress, with a standard cutoff score of ≥16
Measure: Short-term psychological impact Time: Measured at day 1, 60, 120A multicenter randomized clinical trial aiming to assess the efficacy of hydroxychloroquine associated to Zinc compared to hydroxychloroquine, in the prevention of Military Health Professionals Exposed to SARS CoV2 in Tunisia
Description: Frequency of confirmed SARS CoV2 infection
Measure: SARS CoV2 infection Time: At 2 months of follow-upDescription: Any COVID-19 related symptoms (cough, fever, headache, vomiting, nausea, dyspnea, diarrhea, smell disorder,conjunctivitis, dizziness)
Measure: COVID-19 symptoms description Time: At 2 months of follow-upDescription: Any adverse event or serious adverse event
Measure: Adverse Events Time: each month up to 2 monthsThis study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.
Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19
Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI) Time: 14 daysDescription: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.
Measure: Number of participants requiring mechanical ventilation for respiratory failure Time: 14 daysRECOVERY is a randomised trial investigating whether treatment with either Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin or Tocilizumab prevents death in patients with COVID-19.
Description: For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.
Measure: All-cause mortality Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of days stay in hospital
Measure: Duration of hospital stay Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of patients who needed ventilation and the number of days it was required
Measure: Need for (and duration of) ventilation Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of patients who needed renal replacement therapy
Measure: Need for renal replacement Time: Within 28 days after randomisationThe researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.
Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.
Measure: cumulative incidence of SARS-CoV-2 infection Time: within 9 weeks from randomizationDescription: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.
Measure: cumulative incidence of severe COVID-19 or death Time: within 12 weeks of randomizationNovel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.
Description: paO2
Measure: Change from Baseline Oxygenation on Day 1 to Day 5 Time: Day 1 of treatment to day 5 of treatmentDescription: FIO2
Measure: Change from Baseline Oxygenation at Day 5 Time: Day 1 of treatment to day 5 of treatmentDescription: Length in hours
Measure: Intensive Care length of stay Time: Day 0 to Day 28Description: Length in hours
Measure: Required Mechanical Ventilation Time: Day 0 to Day 28Description: Length in hours
Measure: Required Oxygen supplementation Time: Day 0 to Day 28Description: Length in hours
Measure: Hospitalization length of Stay Time: Day 0 to Day 28Description: Date of Death
Measure: Mortality Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Ventricular Tachycardia Time: Day 0 to Day 28Description: Cardiologist Diagnostic Documentation
Measure: Cardiac Arrhythmia - Lengthening QTc Time: Day 0 to Day 28We have to be aware of the challenge and concerns brought by 2019-nCoV to our healthcare workers. Front-line healthcare workers can become infected in the management of patients with COVID-19; the high viral load in the atmosphere, and infected medical equipment are sources for the spread of SARS-CoV-2. If prevention and control measures are not in place, these healthcare workers are at great risk of infection and become the inadvertent carriers to patients who are in hospital for other diseases. Nowadays a question that has not yet been clarified by science has been arises: is hydroxychloroquine associated with zinc effective as a prophylaxis for asymptomatic healthcare workers involved in the treatment of suspected or confirmed cases of COVID-19?
Description: Proportion of participants in whom there was a clinical finding of COVID-19, defined as the occurrence of signs and symptoms suggestive of this disease, corroborated by the detection of SARS-CoV-2 through specific examination (RT-PCR) or by serology for antibodies specific (IgM and IgG).
Measure: Proportion of participants in whom there was a clinical finding of COVID-19. Time: Day 50Description: Number of symptomatic COVID-19 infections.
Measure: Symptomatic COVID-19 infections. Time: Day 50Description: Proportion of Healthcare Workers who developed mild, moderate, or severe forms of COVID-19.
Measure: Healthcare Workers who developed mild, moderate, or severe forms of COVID-19. Time: Day 50Description: Measurement of the QT interval through electrocardiogram evaluation.
Measure: Measurement of the QT interval. Time: Day 0, day 15 and day 50Description: Proportion of Healthcare Workers who evolved with widening of the corrected QT interval or with changes in heart rate on the ECG.
Measure: Widening of the corrected QT interval or with changes in heart rate on the ECG. Time: Day 15 and day 50.Description: Comparison of baseline (visit 1) and final (visit 4) values of hematological and biochemical parameters.
Measure: Comparison of hematological and biochemical parameters. Time: Day 50Description: Proportion of occurrence of adverse events reported by Healthcare Workers or verified by the attending physician, or even observed in laboratory tests.
Measure: Occurrence of adverse events. Time: Day 50BACKGROUND Despite drastic quarantine measures, COVID-19 continues to propagate and threatens global healthcare systems by saturating their capacity with high transmissibility and the particularly protracted length of stay needed by those requiring intensive care. Indeed, once patients advance to the ICU, prognosis is poor and it is thus critical to test medications that may prevent complications and reduce viral shedding. i.e. to protect ambulatory patients and their families from complications and transmission and allow them to #StayHome. To date, no treatment has been reliably demonstrated as effective in COVID-19 patients. Hydroxychloroquine (HCQ), a common and well tolerated medication, has shown promise in vitro for reducing viral replication (for SARS-CoV-2 as well as other coronaviruses with pandemic potential such as SARS-CoV-1 and MERS). Since then, several small-scale hospital-based clinical studies have indicated the potential for reduced viral shedding and hospitalisation as well as favourable evolution of lung pathology. If started earlier, this treatment could prevent complications requiring hospitalisation and intensive care, which may not be available in low-income countries. Robust clinical trials are required to assess the potential of HCQ in COVID-19. OBJECTIVES This trial assesses the efficacy of early treatment with HCQ in COVID-19 outpatients to reduce the incidence and severity of complications including secondary hospitalisation, ICU admissions, lung pathology and death. Secondarily, this trial will also assess its efficacy to reduce viral transmission among household contacts during self-quarantine. The clinical data collected in this trial will also be critical in creating early prognostication models to better predict healthcare needs and have evidence-based prioritization of resource allocation, which is especially critical in low-resource settings. METHODS The trial will recruit 800 SARS-CoV-2+ patients and their household contacts at triage sites across Switzerland. Patients included are 1) at risk of poor outcome (comorbidities or >65y) and 2) well enough to self-isolate at home. These patients will be randomised 1:1 in HCQ:Placebo and given 6 days of early treatment (within 24 hours of the SARS-CoV-2 test). Intensive pragmatic multiparameter at-home follow-up (including point-of-care lung ultrasound in some sites) will continue until their outcome (resolution, or complications, such as hospitalisation, ICU admission, death). Household contacts will have before and after serological testing and social distancing knowledge and practices questionnaires to assess risk factors for infections. The household attack rate of new-onset infections can then assess the efficacy of HCQ to prevent transmission.
Description: Proportion of secondary hospitalisations (and their length), ICU admissions (and their length) and deaths.
Measure: Proportion of poor outcomes (in index cases) Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysDescription: Proportion of a household with new seropositivity for SARS-CoV-2
Measure: Secondary household attack rate (in household contacts) Time: From day 0 (diagnosis and enrolment of index case) to 14 days after the outcome of the index case is recorded (recovery, hospitalisation or death): Average of 25 daysDescription: An ordinal scale of disease severity using a visual analogue scale (0-10 where 0 is asymptomatic)
Measure: Subjective disease severity (in index cases) Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysDescription: As recorded during hospitalisation
Measure: Rate of acute respiratory distress syndrome (in index cases) Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysDescription: Measured with lung ultrasound, CT or x-ray
Measure: Severity of radiological lung pathology (in index cases) Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysDescription: An ordinal scale of disease severity using the evolution of clinical biomarkers such as oxygen saturation, respiration rate etc.
Measure: Objective disease severity (in index cases) Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysDescription: Plasma concentrations of HCQ measured by liquid chromatography-tandem mass spectrometry
Measure: Safety: Unintended toxic HCQ accumulation (in index cases) Time: During the period that the subject is considered as COVID-19-positive : Average of 11 daysDescription: Ambulatory ECG and intensive monitoring for adverse events
Measure: Safety: Adverse events (in index cases) Time: During the period that the subject is considered as COVID-19-positive : Average of 11 daysDescription: Visual analogue scores for social distancing practices (0-5, where 0 is no social distancing at all)
Measure: Social distancing knowledge, attitudes and practices amongst index cases and household contacts Time: During the period that the subject is considered as COVID-19-positive: Average of 11 daysThe aim of this study is to reduce COVID-19 related pulmonary complications in adult patients undergoing all types of elective or emergency surgery in a COVID-19 exposed environment. A Trial in Low and Middle Income Countries (LMICs) and A Trial in High Income Countries (HICs)
Description: The primary outcome is any one of the following COVID-19 specific, inpatient, postoperative pulmonary complications: Pneumonia Acute respiratory distress syndrome (ARDS) Death
Measure: Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
Measure: Rate of Pneumonia Time: From randomisation until discharge from hospital, average less than 30 daysDescription: ARDs will be presented and analysed separately as a secondary outcome measure
Measure: Rate of ARDs Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Death will be presented and analysed separately as a secondary outcome measure
Measure: Death rate Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
Measure: Rate of unexpected ventilation Time: From operation until 30 days post operationDescription: Postoperative diagnosis of proven COVID-19 pulmonary complications
Measure: COVID-19 pulmonary complications Time: 30 days post-surgeryDescription: Overall SARS-CoV-2 infected rate (symptomatic and/or asymptomatic)
Measure: Overall SARS-CoV-2 infected rate Time: 30 days post-surgeryDescription: Duration of hospital stay (including time spent in intensive care, time ventilated)
Measure: Duration of hospital stay Time: 30 days post-surgeryDescription: Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale
Measure: Pulmonary function Time: 30 days post-surgeryHydroxychloroquine is widely used to treat autoimmune diseases. Clinical investigation has found that a high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, therefore, hydroxychloroquine as anti-inflammatory agents may reduce this response in accord with their use in autoimmune disease where the cytokine response can be reduced. Favipiravir is an antiviral drug developed in Japan that the data sheet notes that it is a pyrazinecarboxamide derivative with activity against influenza viruses, west nile virus, yellow fever virus, foot and mouth disease virus as well as against flaviviruses, arenaviruses, bunyaviruses and alphaviruses. In February the drug was used for COVID-19 disease in China and was declared effective in treatment, and a report published (in press) comparing Favipiravir with Lopinavir /ritonavir suggested that Favipiravir was superior for prevention of disease progression and viral clearance. The objective of this pilot study is to compare 3 arms: hydroxychloroquine; favipiravir; supportive treatment only, in symptomatic patients infected by SARS-CoV-2 in an open label randomized clinical trial. The difference between groups will allow an effect size to be determined for a definitive clinical trial
Description: Two consecutive negative (SARS-CoV-2 PCR) nasopharyngeal swabs
Measure: Primary outcome measure will be time to viral clearance Time: through study completion up to 21 daysDescription: Implementation of escalation of Respiratory Support
Measure: Requirement of Escalation of Respiratory Support Time: through study completion up to 21 daysDescription: Time frame for presenting symptoms to resolve
Measure: Time until resolution of presenting symptoms Time: through study completion up to 21 daysDescription: Monitor and document all adverse effects during therapy
Measure: Adverse effects Time: through study completion up to 21 daysDescription: Deterioration of clinical condition requiring ICU admission
Measure: Requirement of ICU Admission Time: through study completion up to 21 daysDescription: Mortality rate due to COVID-19
Measure: Mortality rate Time: Mortality will be collected at 28 daysDescription: Determination of the change in lactate levels before and after treatment as a measure of disease activity
Measure: Serum lactate measurement Time: through study completion up to 21 daysDescription: Determination of the change in ferritin levels before and after treatments as a measure of disease activity
Measure: Serum Ferritin measurement Time: through study completion up to 21 daysDescription: Determination of the change in D Dimer levels before and after treatments as a measure of disease activity
Measure: Serum D Dimer measurement Time: through study completion up to 21 daysDescription: Determination of the change in procalcitonin levels before and after treatments as a measure of disease activity
Measure: Serum procalcitonin measurement Time: through study completion up to 21 daysDescription: Determination of the change in brain naturetic peptide levels before and after treatments as a measure of disease activity
Measure: Serum brain naturetic peptide measurement Time: through study completion up to 21 daysDescription: Determination of the change in Ratio of Lymphocyte to Neutrophil, before and after treatments as a measure of disease activity
Measure: Ratio of Lymphocyte to Neutrophil, measurement Time: through study completion up to 21 daysThe antimalarial agent hydroxychloroquine(HCQ) have been used widely used for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These compounds lead to improvement of clinical and laboratory parameters, but their slow onset of action differ them from glucocorticoids and nonsteroidal antiinflammatory agents. Among rheumatic diseases, the primary role of HCQ is in the management of articular and skin manifestations of systemic lupus erythematosus (SLE) and the treatment of mild to moderately active rheumatoid arthritis (RA).
Description: serum level
Measure: immunoglobulin mesurement Time: 1 monthCOVID-19 is an emerging pandemic disease affecting most countries including Senegal, caused by the new coronavirus (SARS-CoV-2) which was first detected in the city of Wuhan in China in December 2019. A rapid spread of the disease has occurred at a global scale, associated with a mortality rate of 3.4%. The first case in Africa was declared on February 15, 2020 in Egypt and the first case in Senegal was declared on March 2nd, 2020. In this context, the SEN-CoV-Fadj clinical trial aims to evaluate efficacy and safety, among adults, of different therapeutic regimens considered optimal according to current knowledge, as well as available and adapted to Sub-Saharan Africa. This trial is nested into a cohort of confirmed cases of COVID-19 in Senegal aiming to understand the main clinical, biological, virologic and immunological characteristics of the infection. The protocol of the cohort is based and adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) / World Health Organization (WHO) Clinical Characterisation Protocol (CCP). Two therapeutic regimens have been eligible in the short term for SEN-CoV-Fadj: Hydroxychloroquine (HCQ) on one hand, and the combination of Hydroxychloroquine and Azithromycin (HCQ + AZM) on the other hand.
Description: Real time-PCR (RT-PCR) result of the naso- and oro-pharyngeal sample
Measure: SARS-CoV-2 viral load level Time: Day 7Background: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.
Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge
Measure: Mean days of hospital stay Time: Three monthsDescription: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.
Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead Time: Three monthsDescription: Daily delta of oxygenation index during the hospitalization
Measure: Mean of oxygenation index delta Time: Three monthsDescription: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.
Measure: Mean time to viral PCR negativization Time: One monthThe host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.
Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 2 Time: At 2 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2 Time: At 2 days after RTDescription: Pa02 / Fi02 > 300 mmHg
Measure: Blood Gas Analysis at Day 2 Time: At 2 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 2 Time: At 2 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 5 Time: At 5 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5 Time: At 5 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 5 Time: At 5 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 7 Time: At 7 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7 Time: At 7 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 7 Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7 Time: At 7 days after RTDescription: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)
Measure: Recovery time Time: From RT administration until hospital discharge or deathDescription: COVID-19 negativization test
Measure: COVID-19 status Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1 Time: At 1 month after RTDescription: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.
Measure: Acute Toxicity Time: 1-3 months after RTMany reports argued about the possible beneficial effects of Hydroxychloroquine in treating COVID-19 patients and this study was designed to investigate this claim
Description: PCR will be done every 72 h day till 2 consecutive negative PCR tests(24h apart) which is the viral clearance.The time between randomization and viral clearance is the viral clearance time
Measure: time to viral clearance Time: 21 days after patients randomizationDescription: total number of deaths divided by total number of the group
Measure: % of mortality Time: 60 days after randomizationDescription: time from patients randomization till discharge
Measure: Length of stay Time: 60 days after randomizationDescription: time from randomization till day of fever subsiding
Measure: time to be afebrile Time: 60 days after randomizationDescription: %of deteriorated patients necessitates mechanical ventilation
Measure: need for mechanical ventilation Time: 60 days after randomizationOlder adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.