Name (Synonyms) | Correlation | |
---|---|---|
drug683 | Mavrilimumab Wiki | 0.18 |
drug1422 | vv-ECMO only (no cytokine adsorption) Wiki | 0.18 |
drug1421 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.18 |
drug850 | Placebo Wiki | 0.13 |
drug103 | Awake Prone Positioning Wiki | 0.12 |
drug796 | Ophthalmologic exam Wiki | 0.12 |
drug784 | Observational only Wiki | 0.12 |
drug480 | Helmet CPAP Wiki | 0.12 |
drug495 | Hospital anxiety and depression scale Wiki | 0.12 |
drug569 | Immunological profiling Wiki | 0.12 |
drug595 | Intermittent prone positioning instructions Wiki | 0.12 |
drug919 | Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki | 0.12 |
drug1001 | SPIN-CHAT Program Wiki | 0.12 |
drug681 | Matching placebo Wiki | 0.12 |
drug1222 | Ventil - a gas flow divider Wiki | 0.12 |
drug448 | Fondaparinux Wiki | 0.12 |
drug857 | Placebo PBMT/sMF Wiki | 0.12 |
drug1254 | Zilucoplan® Wiki | 0.12 |
drug994 | SARS-CoV2 serum antibody testing Wiki | 0.12 |
drug1080 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki | 0.12 |
drug489 | High Flow Nasal Oxygen (HFNO) Wiki | 0.12 |
drug474 | HFNC Wiki | 0.12 |
drug1295 | conventional oxygen Wiki | 0.12 |
drug1073 | Standard of care. Wiki | 0.12 |
drug1078 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki | 0.12 |
drug511 | Hydroxychloroquine + azithromycin + / - tocilizumab Wiki | 0.12 |
drug980 | Ruxolitinib plus simvastatin Wiki | 0.12 |
drug470 | HCQ & AZ vs HCQ+SIR Wiki | 0.12 |
drug1214 | Usual care positioning with no instructions Wiki | 0.12 |
drug1183 | Treatment with Dexmedetomidine Wiki | 0.12 |
drug226 | COVID-19+ observational Wiki | 0.12 |
drug887 | Postural Positioning Wiki | 0.12 |
drug24 | ABX464 Wiki | 0.12 |
drug385 | ECCO2R Wiki | 0.12 |
drug1181 | Treatment and prophylaxis Wiki | 0.12 |
drug339 | DFV890 Wiki | 0.12 |
drug550 | Hyperbaric oxygen Wiki | 0.12 |
drug44 | Airway pressure release ventilation Wiki | 0.12 |
drug123 | BCG-Denmark Wiki | 0.12 |
drug781 | Observation only Wiki | 0.12 |
drug902 | Prone Positioning Wiki | 0.12 |
drug158 | Biological sampling Wiki | 0.12 |
drug354 | Defibrotide Injection Wiki | 0.12 |
drug1400 | standard operating procedures Wiki | 0.12 |
drug1386 | remdesivir Wiki | 0.12 |
drug930 | Questionnaires, spirometry Wiki | 0.12 |
drug854 | Placebo Administration Wiki | 0.12 |
drug396 | Eicosapentaenoic acid gastro-resistant capsules Wiki | 0.12 |
drug39 | Active PBMT/sMF Wiki | 0.12 |
drug121 | BCG GROUP Wiki | 0.12 |
drug18 | 2: Usual practice + SYMBICORT RAPIHALER Wiki | 0.12 |
drug571 | Impact Event Score Wiki | 0.12 |
drug689 | Mefloquine + azithromycin + / - tocilizumab Wiki | 0.12 |
drug65 | Angiotensin Receptor Blockers Wiki | 0.12 |
drug230 | CPAP Wiki | 0.12 |
drug686 | Medical Ozone procedure Wiki | 0.12 |
drug1416 | trimethoprim/sulfamethoxazole Wiki | 0.12 |
drug588 | Interferon beta 1a Wiki | 0.12 |
drug1058 | Standard Public Health measures Wiki | 0.12 |
drug1079 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki | 0.12 |
drug1247 | XCEL-UMC-BETA Wiki | 0.12 |
drug673 | Machine learning model Wiki | 0.12 |
drug64 | Angiotensin 1-7 Wiki | 0.12 |
drug481 | Helmet Continuous Positive Airway Pressure (CPAP) Wiki | 0.12 |
drug12 | 1: Usual practice Wiki | 0.12 |
drug1339 | mechanical ventilation Wiki | 0.12 |
drug52 | Alteplase 100 MG [Activase] Wiki | 0.12 |
drug663 | MAS825 Wiki | 0.12 |
drug375 | Dociparastat sodium Wiki | 0.12 |
drug1369 | patients receiving nasal high flow Wiki | 0.12 |
drug51 | Almitrine Wiki | 0.12 |
drug343 | Dapagliflozin 10 MG Wiki | 0.12 |
drug714 | Multiple Doses of Anti-SARS-CoV-2 convalescent plasma Wiki | 0.12 |
drug1165 | Tirofiban Injection Wiki | 0.12 |
drug1011 | Sargramostim Wiki | 0.12 |
drug154 | Biological collection (patients co infected HIV Sras-CoV-2) Wiki | 0.12 |
drug482 | Helmet non-invasive ventilation (NIV) Wiki | 0.12 |
drug678 | Masimo, LidCO Wiki | 0.12 |
drug800 | Organicell Flow Wiki | 0.12 |
drug98 | Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki | 0.12 |
drug475 | HFNO Wiki | 0.12 |
drug1412 | this study is non- interventional Wiki | 0.12 |
drug1081 | Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki | 0.12 |
drug756 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.12 |
drug53 | Alteplase 50 MG [Activase] Wiki | 0.12 |
drug1307 | gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki | 0.12 |
drug1070 | Standard of care therapies Wiki | 0.12 |
drug677 | Marker Therapeutics D2000 Cartridge (D2000) for use with the Spectra Optia® Apheresis System (Optia SPD Protocol) Wiki | 0.12 |
drug1065 | Standard of Care (SoC) Wiki | 0.12 |
drug688 | Mefloquine Wiki | 0.12 |
drug814 | PLACEBO GROUP Wiki | 0.12 |
drug38 | Acetylsalicylic acid Wiki | 0.12 |
drug282 | Clopidogrel Wiki | 0.12 |
drug920 | Quality of Life Wiki | 0.12 |
drug160 | Biological/Vaccine: Angiotensin peptide (1-7) derived plasma Wiki | 0.12 |
drug505 | Hydroxychloroquine Wiki | 0.11 |
drug108 | Azithromycin Wiki | 0.09 |
drug446 | Follow up Wiki | 0.09 |
drug365 | Dexamethasone injection Wiki | 0.09 |
drug903 | Prone position Wiki | 0.09 |
drug264 | Chloroquine Sulfate Wiki | 0.09 |
drug957 | Remdesivir Wiki | 0.07 |
drug1062 | Standard of Care Wiki | 0.07 |
drug694 | Mesenchymal Stromal Cells Wiki | 0.07 |
drug303 | Control Wiki | 0.06 |
drug872 | Placebos Wiki | 0.06 |
drug140 | Baricitinib Wiki | 0.06 |
drug1003 | Saline Wiki | 0.06 |
drug801 | Oseltamivir Wiki | 0.06 |
drug1060 | Standard care Wiki | 0.06 |
drug612 | Ivermectin Wiki | 0.05 |
drug60 | Anakinra Wiki | 0.05 |
drug1373 | placebo Wiki | 0.04 |
drug522 | Hydroxychloroquine Sulfate Wiki | 0.04 |
drug647 | Lopinavir/ritonavir Wiki | 0.04 |
drug865 | Placebo oral tablet Wiki | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
D011665 | Pulmonary Valve Insufficiency NIH | 0.25 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.19 |
D007249 | Inflammation NIH | 0.16 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.16 |
D055371 | Acute Lung Injury NIH | 0.15 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.14 |
D011014 | Pneumonia NIH | 0.14 |
D018352 | Coronavirus Infections NIH | 0.13 |
D012594 | Scleroderma, Localized NIH | 0.12 |
D012595 | Scleroderma, Systemic NIH | 0.12 |
D005128 | Eye Diseases NIH | 0.12 |
D012818 | Signs and Symptoms, Respiratory NIH | 0.12 |
D012120 | Respiration Disorders NIH | 0.09 |
D011024 | Pneumonia, Viral NIH | 0.09 |
D007239 | Infection NIH | 0.09 |
D012598 | Scoliosi NIH | 0.09 |
D012141 | Respiratory Tract Infections NIH | 0.09 |
D013577 | Syndrome NIH | 0.08 |
D012140 | Respiratory Tract Diseases NIH | 0.08 |
D000860 | Hypoxia NIH | 0.08 |
D016769 | Embolism and Thrombosis NIH | 0.07 |
D003141 | Communicable Diseases NIH | 0.07 |
D004617 | Embolism NIH | 0.06 |
D008171 | Lung Diseases, NIH | 0.05 |
D013927 | Thrombosis NIH | 0.04 |
D055370 | Lung Injury NIH | 0.03 |
D016638 | Critical Illness NIH | 0.03 |
D014777 | Virus Diseases NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0010444 | Pulmonary insufficiency HPO | 0.25 |
HP:0002090 | Pneumonia HPO | 0.14 |
HP:0000478 | Abnormality of the eye HPO | 0.12 |
HP:0012344 | Morphea HPO | 0.12 |
HP:0011947 | Respiratory tract infection HPO | 0.09 |
HP:0012418 | Hypoxemia HPO | 0.08 |
HP:0002088 | Abnormal lung morphology HPO | 0.05 |
HP:0001907 | Thromboembolism HPO | 0.04 |
There are 65 clinical trials
This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.
Description: Time (hours) from randomization to recovery defined as 1) absence of fever, as defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications AND 2) absence of symptoms of greater than mild severity for 24 hours AND 3) not requiring supplemental oxygen beyond pre-COVID baseline AND 4) freedom from mechanical ventilation or death
Measure: Hours to recovery Time: 42 daysDescription: Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications
Measure: Time fever resolution Time: 42 daysTo develop and validate a machine-learning model based on clinical, laboratory, and radiological characteristics alone or combination of COVID-19 patients to facilitate risk Assessment before and after symptoms and triage (home, hospitalization inward or ICU).
Description: AUC, accuracy, sensitivity, and specificity
Measure: Predictive performance Time: Janunary 1, 2020, to February 13, 2020The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysDescription: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, IL-2, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30We hypothesize that inhaled steroid therapy and long acting beta 2 adrenergic agonist, widely prescribed in asthma patients, may also have a local protective effect against coronavirus infection, even in patients without asthma. The primary purpose is To compare time to clinical improvement in patients receiving standard of care associated to the combination budesonide/formoterol or standard of care only. Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days.
Description: Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days. The seven-category ordinal scale consisted of the following categories: Not hospitalized with resumption of normal activities Not hospitalized, but unable to resume normal activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death. These parameters will be evaluated daily during hospitalization.
Measure: Time (in days) to clinical improvement within 30 days after randomization Time: within 30 daysNon tuberculous mycobacteria (NTM), Burkholdria spp, Aspergillus in the lung are almost impossible to eradicate with conventional antibiotics. In addition COVID-19 has know current treatment. These patients have few options to treat their lung infection. Nitric oxide has broad bactericidal and virucidal properties. It has been shown that nitric oxide was safe to be inhaled for similar cystic fibrosis patients and reduced drug resistant bacteria in the lungs. Further, research indicates that clinical isolates of NTM, Burkholderia spp, Aspergillus spp and Corona-like viruses can be eradicated by 160ppm NO exposure in the laboratory petri dish. This is not the first time inhaled NO treatment has been used in patients with difficult lung infections. This study will provide more data to see if NO therapy can reduce the bacterial load in the lungs, help the patients breath better; and in the case of COVID-19 act as a anti-viral agent resulting in the reduction of incidence of oxygen therapy, mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Description: Measure the number of unanticipated adverse events over the duration of the study protocol
Measure: Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects Time: 26 DaysDescription: Measure the change in absolute FEV1.0 change from baseline during 160 ppm inhalation therapy
Measure: Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects Time: Day 5,12,19 and 26Description: Measure the difference from baseline NTM species bacterial load (0 to +4) in sputum during 160ppm nitric oxide inhalation therapy
Measure: Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum Time: Day 19 and 26Description: Measure the difference from baseline CRISS (0-100) during 160ppm nitric oxide inhalation therapy (lower score represents higher quality of life)
Measure: Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score Time: Day 19 and 26Description: Measuring reduction in the incidence of mechanical assistance including oxygen therapy, BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Measure: Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions Time: Day 26Description: Measured by death from all causes
Measure: Efficacy in reduction of mortality Time: Day 26Description: Assessed by time to negative conversion of COVID-19 RT-PCR from upper respiratory tract
Measure: Antiviral effect Time: Day 26Description: Time to clinical recovery as measured by resolution of clinical signs
Measure: Efficacy on clinical improvement Time: Day 26Description: Measured by change in the Modified Jackson Cold Score
Measure: Efficacy on the respiratory symptoms Time: Day 26SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.
Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)
Measure: Ordinal Scale for Clinical Improvement Time: Day 1 to day 28Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 2 to day 28Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 1 to day 28Description: Time to clinical improvement
Measure: Time to clinical improvement Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hoursDescription: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity Time: Day 1 to day 28Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
Measure: Changes in daily breathlessness, cough and sputum scale (BCSS) Time: Day 1 to day 28Description: Looking at blood pressure measured in mmHg
Measure: Safety and tolerability - blood pressure II. Viral load Time: Day 1 to day 28Description: Looking at heart rate measured in beats per minute
Measure: Safety and tolerability - heart rate II. Viral load Time: Day 1 to day 28Description: Looking at temperature measured in degrees Celsius
Measure: Safety and tolerability - temperature II. Viral load Time: Day 1 to day 28Description: Looking at respiratory rate measure in breaths per minute
Measure: Safety and tolerability - respiratory rate II. Viral load Time: Day 1 to day 28Description: Looking at oxygen levels measured in a %
Measure: Safety and tolerability - oxygen saturation II. Viral load Time: Day 1 to day 28Description: Looking at adverse events (numbers and terms)
Measure: Safety and tolerability - adverse events II. Viral load Time: Day 1 to day 28Description: Looking at concomitant medications given during treatment
Measure: Safety and tolerability - concomitant medications II. Viral load Time: Day 1 to day 28Background: 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 monthRandomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.
Description: Number of patients who died, by treatment group
Measure: All-cause mortality at day 28 Time: Day 28Description: Number of patients with treatment-emergent adverse events, by treatment group
Measure: Safety of WJ-MSC Time: Day 28Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group
Measure: Need for treatment with rescue medication Time: Day 28Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group
Measure: Need and duration of mechanical ventilation Time: Day 28Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.
Measure: Ventilator free days Time: Day 28Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.
Measure: Evolution of PaO2 / FiO2 ratio Time: Day 28Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.
Measure: Evolution of the SOFA index Time: Day 28Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.
Measure: Evolution of the APACHE II score Time: Day 28Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.
Measure: Duration of hospitalization Time: Day 28Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.
Measure: Evolution of markers of immune response (leucocyte count, neutrophils) Time: Day 28Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date
Measure: Feasibility of WJ-MSC administration Time: Day 28Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.
Measure: Feasibility of WJ-MSC administration Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: D-dimer Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: Ferritin Time: Day 28Description: Blood sample analysis
Measure: Analysis of subpopulations of lymphocytes and immunoglobulins Time: Day 28Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)
Measure: Evaluation of the in vitro response of the receptor lymphocytes Time: Day 28Description: Reactivity will be assessed using ELISPOT
Measure: Study of reactivity against SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis
Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis for the patient's genomic sequencing
Measure: Genetic variability of patient's genotype in response to treatment Time: Day 28Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample
Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment Time: Day 28The Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY) study is a pragmatic prospective, open-label, randomised controlled trial. CLARITY aims to examine the effectiveness of angiotensin II receptor blockers (ARBs) on improving the outcomes of people who tested positive for COVID-19 disease.
Description: To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; 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 extracorporeal membrane oxygenation (ECMO); Death;
Measure: 7-Point National Institute of Health Clinical Health Score Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; 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 extracorporeal membrane oxygenation (ECMO); Death;
Measure: 7-Point National Institute of Health Clinical Health Score Time: 15 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Measure: Mortality Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Measure: Mortality Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission
Measure: Intensive Care Unit Admission Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission
Measure: Intensive Care Unit Admission Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission
Measure: Intensive Care Unit Admission Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
Measure: Respiratory Failure Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
Measure: Dialysis Requirement Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Measure: Hospitalisation Days Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Measure: Hospitalisation Days Time: 90 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
Measure: Ventilator-Free Days Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
Measure: Dialysis Days Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes risk of acute kidney injury, based on the idney Disease: Improving Global Outcomes definition
Measure: Acute Kidney Injury Time: 28 DaysDescription: To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors
Measure: Hypotension Requiring Vasopressors Time: 90 DaysThis is a quality improvement study with the purpose of observing and measuring the effects of implementation of a proven standardized lung protective ventilation protocol in the new electronic medical record system iCentra across all Intermountain Healthcare hospitals. Approximately 14,000 records will be accessed for this study from a database of mechanically ventilated patients established for quality improvement purposes. The investigators hypothesize that implementation of a standardized computerized lung protective ventilation protocol across all Intermountain Healthcare hospitals will be feasible, will decrease initial tidal volumes to the target 6 ml/kg PBW, and will improve outcomes. The objectives of this study are to: - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in patients with acute respiratory failure requiring mechanical ventilation - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in the sub-group of patients with the acute respiratory distress syndrome (ARDS) - Measure compliance with the implementation of a computerized lung protective ventilation protocol at 12 Intermountain Healthcare hospitals
In December 2019 a new kind of virus was identified in China as the responsible of severe acute respiratory syndrome (SARS) and interstitial pneumonia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread around the world and in February 2020 became a pandemia in Europe. No pharmacological treatment is actually licensed for the SARS-CoV2 infection and at the current state of art there is a lack of data about the clinical management of the coronavirus 2019 disease (COVID-19). The aim of this observational study is to collect the data and the outcomes of COVID-19 patients admitted in the H. Sacco Respiratory Unit treated according to the Standard Operating Procedures and the Good Clinical Practice.
Description: Data collection about the real life management of patients affected by SARS-CoV-2 infection with acute respiratory distress syndrome
Measure: Real life data of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection Time: 1-6 monthsDescription: How many patients died during the hospitalization
Measure: in-hospital mortality Time: 1 monthDescription: How many patients died 30 days after the discharge
Measure: 30 days mortality Time: 1 monthDescription: How many patients died 6 months after the discharge
Measure: 6 months mortality Time: 6 monthsDescription: How many patients were intubated during the hospitalization
Measure: Intubation rate Time: 7 daysDescription: How many days/hours from admittance to intubation
Measure: Time to Intubation Time: 7 daysDescription: How many days/hours from admittance to the start of non invasive ventilation or CPAP therapy
Measure: Time to ventilation Time: 7 daysDescription: How many days/hours from the start of non invasive ventilation or CPAP therapy to the intubation
Measure: Non invasive to Invasive time Time: 7 daysDescription: How many patients were healed from the infection and discharged
Measure: Recovery rate Time: 1 monthDescription: How many patients underwent re-infection after previous recovery from COVID19
Measure: Recurrence rate Time: 1 monthDescription: Assessment of the risk factors for the infection and the admission to the hospital
Measure: Risk factor for COVID19 Time: retrospectiveDescription: What serological parameter could be used as predictor of good or negative prognosis.
Measure: Blood tests and outcome Time: 1 monthDescription: Impact of antiviral therapy on the clinical course of the disease
Measure: Antiviral therapy Time: 1 monthDescription: Assessment of bacterial, fungal or other coinfections rate
Measure: Coinfections Time: 1 monthDescription: Impact of radiological findings on the clinical course and the outcome
Measure: Radiological findings Time: 1 monthDescription: Impact of ultrasound findings on the clinical course and the outcome
Measure: Ultrasound findings Time: 1 monthDescription: Assessment of the evidence of myocardial injury in covid19+ patients
Measure: Myocardial injury Time: 1 monthDescription: impact of standard therapeutic operating procedures (eg enteral nutrition, hydration, drugs) on the clinical course.
Measure: Medical management Time: 1 monthThe emergence of SARS-CoV-2 is currently engaging and consuming most of resources of efficient healthcare systems in Europe, and several hospitals are currently experiencing a shortage of ICU beds for critically-ill patients with SARS-CoV-2 pneumonia. A risk stratification based on clinical, radiological and laboratory parameters seems necessary in order to better identify those patients who may need ICU admission and/or those who may benefit from a prompt antiviral therapy
Description: Composite of ICU admission or SpO2<92% with 100% FiO2 of oxygen treatment (reservoir mask or CPAP or NIV), respiratory rate >30 bpm, respiratory distress
Measure: Respiratory failure Time: 14 daysDescription: Incidence of bacterial superinfection among ventilated patients with SARS-CoV-2 pneumonia
Measure: Occurence of bacterial superinfection Time: 14 daysIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: interleukin-6 (IL-6) level after 72 hours Time: 72 hoursDescription: survival after 30 days
Measure: 30-day-survival Time: 72 hoursDescription: needed dosage of norepinephrine and other vasopressors
Measure: vasopressor dosage Time: 72 hoursDescription: fluid balance levels during cytokine adsorption
Measure: fluid balance Time: 72 hoursDescription: serum-lactate levels during cytokine adsorption
Measure: lactate Time: 72 hoursPhase IV study to evaluate the effectiveness of additional inhaled sargramostim (GM-CSF) versus standard of care on blood oxygenation in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure.
Description: by mean change in PaO2/FiO2 (PaO2=Partial pressure of oxygen; FiO2= Fraction of inspired oxygen)
Measure: Improvement in oxygenation at a dose of 250 mcg daily during 5 days improves oxygenation in COVID-19 patients with acute hypoxic respiratory failure Time: at end of 5 day treatment periodDescription: demonstrated by bacterial or fungal culture
Measure: incidence of severe or life-threatening bacterial, invasive fungal or opportunistic infection Time: during hospital admission (up to 28 days)Description: defined by HS (Hemophagocytic Syndrome) score
Measure: number of patients developing features of secondary haemophagocytic lymphohistiocytosis Time: at enrolment, end of 5 day treatment period, 10 day period, 10-20 weeksCOVID-19 may cause severe pneumonitis that require ventilatory support in some patients, the ICU mortality is as high as 62%. Hospitals do not have enough ICU beds to handle the demand and to date there is no effective cure. We explore a treatment administered in a randomized clinical trial that could prevent ICU admission and reduce mortality. The overall hypothesis to be evaluated is that HBO reduce mortality, increase hypoxia tolerance and prevent organ failure in patients with COVID19 pneumonitis by attenuating the inflammatory response.
Description: The proportion of subjects admitted to ICU from day 1 to day 30, based on at least one of the following criteria: i) Rapid progression over hours ii) Lack of improvement on high flow oxygen >40L/min or non invasive ventilation with fraction of inspired oxygen (FiO2) > 0.6 iii) Evolving Hypercapnia or increased work of breathing not responding to increased oxygen despite maximum standard of care available outside ICU iv) Hemodynamic instability or multi organ failure with maximum standard of care available outside ICU
Measure: ICU admission Time: Through study completion 30 daysDescription: Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30.
Measure: 30-day mortality Time: Through study completion 30 daysDescription: Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30
Measure: Time-to-intubation Time: Through study completion 30 daysDescription: Time-to-ICU, i.e. cumulative ICU free days, derived as the number of days from day 1 to ICU, where all ICU free subjects are censored at day 30.
Measure: Time-to-ICU Time: Through study completion 30 daysDescription: Mean change in inflammatory response from day 1 to day 30. White cell count + differentiation Procalcitonin C-Reactive protein Cytokines (IL-6) (if available at local laboratory) Ferritin D-Dimer LDH
Measure: Inflammatory response Time: Through study completion 30 daysDescription: Overall survival (Kaplan-Meier)
Measure: Overall survival Time: Through study completion 30 daysDescription: Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.
Measure: Hospital mortality Time: Through study completion 30 daysDescription: Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30.
Measure: ICU mortality Time: From ICU admission to study completion 30 daysDescription: Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.
Measure: Time in Invasive Ventilation Time: From ICU admission to study completion 30 daysDescription: Mean daily NEWS from day 1 to day 30.
Measure: NEWS Time: Through study completion 30 daysDescription: Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.
Measure: PaO2/FiO2 (PFI) Time: Through study completion 30 daysDescription: Proportion of HBO treatments given vs planned. Proportion of subjects with HBO treatment administered within 24h after enrolment.
Measure: HBO Compliance Time: Day 1 to day 7Description: Time-to-discharge from hospital
Measure: Hospital discharge Time: Through study completion 30 daysDescription: Mean oxygen dose per day including HBO and cumulative pulmonary oxygen toxicity expressed as Units of oxygen pulmonary toxicity dose (UPTD) and Cumulative pulmonary toxicity dose (CPTD) from day 1 to day 30.
Measure: Oxygen dose Time: Through study completion 30 daysDescription: Median number of HBO treatments and dose of HBO given, from day 1 to day 7
Measure: HBO dose Time: Day 1 to day 7Description: Change in expression of Micro RNA in plasma from day 1 to day 30
Measure: Micro RNA Time: Through study completion 30 daysDescription: Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) (20 Subjects) from day 1 to day 30
Measure: Hypoxic response Time: Through study completion 30 daysDescription: Immunological response (20 subjects) from day 1 to day 30 in the following. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα) Lymphocyte profile Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα), T-reg cells (CD3+/CD4+/CD25+/CD127+) Monocyte proliferation markers, Ex vivo monocyte function
Measure: Immunological response Time: Through study completion 30 daysDescription: Mean change in routine biomarkers for organ dysfunction, from day 1to day 30.
Measure: Multi organ dysfunction Time: Through study completion 30 daysDescription: Viral load, review of records from day 1 to day 30.
Measure: Viral load Time: Through study completion 30 daysDescription: Number of secondary infections, review of records, number of events and patients from day 1 to day 30.
Measure: Secondary infections Time: Through study completion 30 daysDescription: Diagnosed PE needing treatment, review of records, number of events and patients from day 1 to day 30.
Measure: Pulmonary embolism Time: Through study completion 30 daysDescription: Changes on Pulmonary CT, review of records from day 1 to day 30.
Measure: Pulmonary CT Time: Through study completion 30 daysDescription: Changes on Chest X-ray, review of records from day 1 to day 30.
Measure: Chest X-ray Time: Through study completion 30 daysDescription: Changes in Lung ultrasound, review of records from day 1 to day 30.
Measure: Lung ultrasound Time: Through study completion 30 daysBackground: A novel Coronavirus (SARS-CoV-2) described in late 2019 in Wuhan, China, has led to a pandemic and to a specific coronavirus-related disease (COVID-19), which is mainly characterized by a respiratory involvement. While researching for a vaccine has been started, effective therapeutic solutions are urgently needed to face this threaten. The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host 's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that is downregulated in COVID-19 patient and it may potentially improve respiratory function in this setting. Methods/Design: The Investigators describe herein the methodology of a randomized, controlled, adaptive Phase II/Phase III trial to test the safety, efficacy and clinical impact of the infusion of angiotensin-(1-7) in COVID-19 patients with respiratory failure requiring mechanical ventilation. A first phase of the study, including a limited number of patients (n=20), will serve to confirm the safety of the study drug, by observing the number of the severe adverse events. In a second phase, the enrollment will continue to investigate the primary endpoint of the study (i.e. number of days where the patient is alive and not on mechanical ventilation up to day 28) to evaluate the efficacy and the clinical impact of this drug. Secondary outcomes will include the hospital length of stay, ICU length of stay, ICU and hospital mortality, time to weaning from mechanical ventilation, reintubation rate, secondary infections, needs for vasopressors, PaO2/FiO2 changes, incidence of deep vein thrombosis, changes in inflammatory markers, angiotensins plasmatic levels and changes in radiological findings. The estimated sample size to demonstrate a reduction in the primary outcome from a median of 14 to 11 days is 56 patients, 60 including a dropout rate of 3% (i.e. 30 per group), but a preplanned recalculation of the study sample size is previewed after the enrollment of 30 patients. Expected outcomes/Discussion: This controlled trial will assess the efficacy, safety and clinical impact of the Angiotensin-(1-7) infusion in a cohort of COVID-19 patients requiring mechanical ventilation. The results of this trial may provide useful information for the management of this disease.
Description: composite outcome of mortality and necessity of mechanical ventilation
Measure: ventilator free days Time: 28 daysDescription: number of days free from intensive care unit
Measure: ICU free days Time: trough study completion, on average 40 daysDescription: Hospital length of stay
Measure: Hospital length of stay Time: through study completion, on average 60 daysDescription: Time to wean from mechanical ventilation
Measure: Time to wean from mechanical ventilation Time: through study completion, on average 14 daysDescription: PaO2/FiO2 changes during drug administration
Measure: PaO2/FiO2 changes during drug administration Time: 48 hoursDescription: US confirmed deep vein thrombosis
Measure: Deep vein thrombosis incidence Time: through study completion, on average 30 daysDescription: including IL-1, IL-2, IL-6, IL-7, IL-8, IL-10, TNF-alpha, interferon gamma
Measure: Changes in inflammatory markers Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Ang II and Ang-(1-7) plasmatic levels
Measure: RAS effectors levels Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Chest x-ray or CT scan changes
Measure: Radiological findings Time: through study completion, on average 30 daysDescription: phase 2b = principal safety outcome; phase 3 = secondary outcome
Measure: Rate of serious adverse events Time: study drug administration/day 28 or ICU discharge or deathPhase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study
Description: To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia. Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); transfer to the intensive care unit; death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start.
Measure: to able to reduce the progression of acute respiratory failure Time: 14 daysDescription: To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Measure: Adverse events Time: 7 daysDescription: evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection
Measure: duration of hospitalization Time: 14 daysDescription: To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide. performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress.
Measure: systemic inflammation Time: 14 daysDescription: To evaluate the overall survival at day+28 after start treatment with Defibrotide
Measure: overall survival Time: 28 daysTrial 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 daysCOVID-19 is a respiratory illness caused by SARS-CoV-2 with a range of symptoms from mild, self-limiting respiratory tract infections to severe progressive pneumonia, multiorgan dysfunction and death. A portion of individuals with COVID-19 experience life-threatening hypoxia requiring supplemental oxygen and mechanical ventilation. Management of hypoxia in this population is complicated by contraindication of non-invasive ventilation and limitations in access to mechanical ventilation and critical care staff given the clinical burden of disease. Positional therapy is readily deployable and may ultimately be used to treat COVID-19 related respiratory failure in resources limited settings; and, it has been demonstrated to improve oxygenation and is easy to implement in the clinical setting. The overall goal of this randomized controlled trial is to establish the feasibility of performing a randomized trial using a simple, minimally invasive positional therapy approach to improve hypoxia and reduce progression to mechanical ventilation. The objectives are to examine the effectiveness and feasibility of maintaining an inclined position in patients with confirmed or suspected COVID-19 associated hypoxemic respiratory failure. The investigators hypothesize that (1) oxyhemoglobin saturation will improve with therapy, (2) participants will tolerate and adhere to the intervention, and that (3) participants who adhere to positional therapy will have reduced rates of mechanical ventilation at 72 hours. If successful, this feasibility trial will demonstrate that a simple, readily deployed nocturnal postural maneuver is well tolerated and reverses underlying defects in ventilation and oxygenation due to COVID-19. It will also inform the design of a pivotal Phase III trial with estimates of sample sizes for clinically relevant outcomes.
Description: Number of participants needing mechanical ventilation over total number of participants per arm.
Measure: Incidence of Mechanical Ventilation Time: 72 hoursDescription: Percentage of time participants stay in the assigned position will be used to determine adherence.
Measure: Percentage of time in the assigned position Time: 72 hoursDescription: Number of participants with supplemental oxygen requirements.
Measure: Number of participants with supplemental oxygen requirements Time: 72 hoursDescription: Mean oxyhemoglobin saturation (percentage) measured over a 24-hour period.
Measure: Change in mean oxyhemoglobin saturation Time: At 24, 48 and 72 hoursDescription: Mean oxyhemoglobin saturation (percentage) measured over an 8-hour period (between 10pm and 6am).
Measure: Change in Nocturnal Oxyhemoglobin saturation Time: Measured between 10pm and 6am daily, up to 72 hoursDescription: Heart Rate (beats per minute) on Routine Vital Sign Assessment.
Measure: Change in Heart Rate Time: At 10, 24, 48 and 72 hoursDescription: Respiratory Rate (cycles per minute) on Routine Vital Sign Assessment.
Measure: Change in Respiratory Rate Time: At 10, 24, 48 and 72 hoursDescription: Mean oxyhemoglobin saturation (percentage) during final 7 minutes in a position.
Measure: Acute change in oxyhemoglobin saturation Time: During the final 7 minutes at each position, up to 72 hoursThe main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival. The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
Description: The time-to-death from all causes within the first 60 days after randomization.
Measure: The time-to-death from all causes Time: day-60Description: the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.
Measure: The time to need for mechanical ventilation (MV) Time: day-28.Description: The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)
Measure: The viral load in the respiratory tract Time: day-10Description: Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28
Measure: Number of patient with at least one episode of healthcare-associated infections Time: day-28Description: To compare the exposition to mechanical ventilation
Measure: Number of days alive without mechanical ventilation Time: day-28Description: Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)
Measure: Measure of SOFA score Time: day-28Description: to compare the exposition to renal replacement therapy
Measure: Number of days alive without renal replacement therapy Time: day-28Description: To compare the lengths of ICU
Measure: Lengths of ICU-stay Time: day-60Description: To compare the lengths of hospital-stay
Measure: Lengths of hospital-stay Time: day-60Description: Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation
Measure: Number of patients with severe hypoxemia, Time: day 60Description: Proportion of patients with cardiac arrest within 1 hour after intubation
Measure: Number of patients with cardiac arrest within 1 hour after intubation Time: day 60This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs). Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells. The purpose of this study is to see if MSCs can help to treat respiratory infections caused by SARS-CoV-2.
Description: Incidence of unexpected adverse events within 28 days following infusion of MSCs. Adverse events are graded by CTCAE version 5.
Measure: Incidence of unexpected adverse events Time: 28 days post cell infusionDescription: Proportion of patients with improved oxygenation, defined as oxygen saturation >=93% on room air or no more than 5L of supplemental oxygen.
Measure: Improved oxygen saturations ≥93% Time: Within 7 days of cell infusionDescription: Decrease in oxygen supplementation assessed by FiO2 % by non-invasive or invasive interventions from baseline to day 7.
Measure: Decrease in oxygen supplementation by non-invasive or invasive interventions Time: Within 7 days of cell infusionDescription: Frequency of patients who progress using mechanical ventilation or ECMO
Measure: Frequency of progression to mechanical ventilation or ECMO Time: 28 days post cell infusionDescription: Days on mechanical ventilation
Measure: Duration of mechanical ventilation Time: Days from time of intubation to extubation or date of death, whichever occurs first, assessed up to 28 days post-infusionDescription: Days of ICU stay
Measure: Duration of ICU stay Time: Days from admission to ICU to discharge from ICU or date of death, whichever occurs first, assessed up to 28 days post-infusionDescription: Days of hospital stay
Measure: Duration of hospital stay Time: Days from admission to hospital to discharge from hospital or date of death, whichever occurs first, assessed up to 28 days post-infusionDescription: Mortality rate from all causes at day 28
Measure: All-cause mortality at day 28 Time: 28 days post cell infusionThe purpose of this national, multicenter service review is to determine and compare ventilation management in COVID-19 patients in the Netherlands, and to whether certain ventilation settings have an independent association with duration of ventilation. In every adult invasively ventilated COVID-19 patient from a particpating ICU, granular ventilator settings and parameters will be collected from start of invasive ventilation for up to 72 hours. Follow up is until ICU and hospital discharge, and until day 90. The primary outcome includes main ventilator settings (including tidal volume, airway pressures, oxygen fraction and respiratory rate). Secondary endpoints are ventilator-free days and alive at day 28 (VFD-28); duration of ventilation; use of proning and recruitment maneuvers; duration of ICU and hospital stay;incidence of kidney injury; and ICU, hospital, 28-day and 90-day mortality.
Description: time between start invasive ventilation and successful extubation in survivors
Measure: Duration of ventilation in survivors; Time: Until 28 days from initiation of mechanical ventilationDescription: Time between admission and discharge ICU or death in ICU
Measure: Duration of ICU stay Time: Until 28 days from initiation of mechanical ventilationDescription: Time between admission and discharge from hospital or death in hospital
Measure: Duration of hospital stay Time: Until 28 days from initiation of mechanical ventilationDescription: Any death during ICU stay
Measure: ICU mortality Time: Until 28 days from initiation of mechanical ventilationDescription: Any death during hospital stay
Measure: Hospital mortality Time: Until 28 days from initiation of mechanical ventilationThe purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.
Description: Estimated by Polymerase chain reaction (PCR)
Measure: The change of viral load in patients with SARS-COVID-19. Time: Upon patient inclusion in the study, after 96 hours and on the 10day;Description: Assessed through the entire patient participation in the study
Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS) Time: up to 8 monthsDescription: The number of days a patient is hospitalized
Measure: Duration of hospitalization Time: through study completion, an average of 8 monthsDescription: Early mortality from all causes will be estimated
Measure: The frequency of early mortality Time: up to 30 daysDescription: Late mortality from all causes will be estimated
Measure: The frequency of late mortality Time: up to 90 daysDescription: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.
Measure: Clinical status at the time of completion of participation in the study Time: through study completion, an average of 8 monthsStudy 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 monthsProne positioning (PP) is an effective first-line intervention to treat moderate-severe acute respiratory distress syndrome (ARDS) patients receiving invasive mechanical ventilation, as it improves gas exchanges and lowers mortality.The use of PP in awake self-ventilating patients with (e.g. COVID-19 induced) ARDS could improve gas exchange and reduce the need for invasive mechanical ventilation, but has not been studied outside of case series.The investigators will conduct a randomized controlled study of patients with COVID-19 induced respiratory failure to determine if prone positioning reduces the need for mechanical ventilation compared to standard management.
Description: A measure of effect of awake prone positioning in reducing requirement for invasive mechanical ventilation.
Measure: The effect of prone positioning on requirement for invasive mechanical ventilation in patients with COVID 19 induced respiratory failure. Time: Up to 28 days post randomisationDescription: Total time spent in prone and supine position as recorded by nurse
Measure: Length of time tolerating prone positioning Time: Daily during intervention up to 28 days post randomisationDescription: Measure of change in oxygenation before intervention
Measure: PaO2/FiO2 measured before prone positioning Time: Immediately before interventionDescription: Measure of change in oxygenation following intervention
Measure: PaO2/FiO2 ratio after 1 hours of prone positioning Time: During interventionDescription: Measure of change in oxygenation using pulse oximetry before intervention where ABG not available
Measure: SpO2/FiO2 ratio measured before prone positioning Time: Immediately before interventionDescription: Measure of change in oxygenation before intervention where ABG not available
Measure: SpO2/FiO2 ratio after 1 hours of prone positioning Time: During InterventionDescription: Escalation of ventilatory support
Measure: Number requiring increase in ventilatory assistance (CPAP+BIPAP+IMV etc) Time: Up to 28 days post randomisationDescription: Measure of work of breathing in COVID-19 based on Oxygen Delivery Device, Oxygen Saturation and respiratory rate and accessory muscle use with 0-3 Mild, 4-6 Moderate and 7-10 Severe
Measure: Work of breathing assessment (Respiratory distress scale) Time: Immediately before and during interventionDescription: Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning
Measure: Changes in bioimpedance measures of lung edema in patients in PP Time: During interventionDescription: Rescue awake prone positioning in control patients in response to hypoxia
Measure: Use of awake prone positioning as a rescue intervention in control patients Time: Up to 28 days post randomisationCOVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine. Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response. Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19. Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection. In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.
Description: Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
Measure: Percentage of patients who develop severe respiratory failure. Time: 7 daysDescription: Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 14 from randomization.
Measure: Percentage of patients who develop severe respiratory failure. Time: 14 daysDescription: Time from ICU admision to ICU discharge.
Measure: Length of ICU stay. Time: 28 daysDescription: Time from hospital admision to hospital discharge.
Measure: Length of hospital stay Time: 28 daysDescription: Percentage of patients alive at 6 months
Measure: Survival rate at 6 months Time: 6 monthsDescription: Percentage of patients alive at 12 months
Measure: Survival rate at 12 months Time: 12 monthsDescription: Percentage of patients who died from any cause 28 days after inclusion in the study
Measure: Survival rate at 28 days Time: 28 daysDescription: Percentage of patients with each AE by grade in relation with total number of treated patients
Measure: Percentage of patients with each AE by grade Time: 28 daysDescription: Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Measure: Percentage of patients who discontinued due to AEs Time: 28 daysThe objective of the study is to evaluate the efficacy of helmet NIV in reducing the duration of invasive mechanical ventilation in order to minimize ventilator needs during the COVID-19 pandemic.
Description: duration of mechanical ventilation via endotracheal tube
Measure: ventilator days Time: up to 4 weeksDescription: number of days admitted to the ICU
Measure: Intensive care unit (ICU) length of stay Time: up to 6 weeksDescription: number of patients requiring endotracheal intubation after extubation
Measure: need for re-intubation Time: up to 6 weeksDescription: number of days spent in hospital during enrollment hospitalization
Measure: hospital length of stay Time: up to 6 weeksDescription: death from any cause during hospitalization time of enrollment
Measure: hospital mortality Time: up to 6 weeksDescription: death from any cause 90 day, 1year
Measure: long term mortality Time: up to 1 yearDescription: including ventilator associated pneumonia, GI hemorrhage, DVT/PE, sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home)
Measure: discharge location Time: up to 90 daysDescription: days alive and institution free
Measure: health care utilization Time: up to 6 weeksDescription: ultrasound measurement at end expiration: enrollment, pre extubation, post extubation
Measure: diaphragm ultrasound thickness Time: up to 6 weeksDescription: ultrasound measurement at end expiration and inspiration to calculate thickening fraction
Measure: diaphragm thickening fraction Time: up to 6 weeksThe current sars-cov-2 epidemic is responsible for severe respiratory infections leading to end-of-life situations. Dexmedetomidine may be indicated in mild to moderate sedation in palliative patients, due to its pharmacological characteristics. The hypothesis of this study is that Dexmedetomidine would allow effective and safe light sedation in patients with respiratory failure in palliative situations suffering from Covid-19 infection.
Description: Number of days of mild to moderate sedation induced by dexmedetomidine until death or change of molecule.
Measure: Efficacy of mild to moderate palliative sedation induced by Dexmedetomidine. Time: Day 30Description: Overall survival time in days from inclusion.
Measure: Overall survival of patients on Dexmedetomidine Time: Day 30Description: The daily effectiveness of Dexmedetomidine on pain assessed by the NCS-R scale (Nociception Coma Scale) : the score is between 0 and 9.
Measure: Daily analgesic effect of Dexmedetomidine Time: Day 30Description: Number of the various sedative molecules used in the subjects of the study in addition to Dexmedetomidine.
Measure: Other sedative pharmacological agents Time: Day 30Description: Daily dosage measurement in ug / kg / h of Dexmedetomidine necessary to obtain light to moderate sedation
Measure: Average dosage required for Dexmedetomidine to achieve mild to moderate sedation Time: Day 30This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.
Description: Respiratory decompensation New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy
Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following: Time: Randomization through Day 30Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge
Measure: Hierarchical composite outcome measures: Time: Randomization through Day 30Description: Time to hospital discharge
Measure: Time to hospital discharge Time: Randomization through Day 30Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation
Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation Time: Randomization through Day 30Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)
Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure) Time: Randomization through Day 30Description: Time to death from any cause
Measure: Time to death from any cause Time: Randomization through Day 30Description: Time to new/worsened organ dysfunction
Measure: Time to new/worsened organ dysfunction Time: Randomization through Day 30Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)
Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline) Time: Randomization through Day 30The study aims to investigate the efficacy of extracorporeal CO2 removal for correction of hypercapnia in coronavirus disease 19 (COVID-19)-associated acute respiratory distress syndrome
Description: Delta partial pressure of carbon dioxide change during ECCO2R treatment
Measure: Delta change in arterial partial pressure of carbon dioxide during ECCO2R treatment Time: Up to 72 hoursDescription: Epinephrine and norepinephrine dose, mcg/kg/min
Measure: Change in vasopressor use during ECCO2R Time: Up to 72 hoursDescription: Assessment of changes in tidal volume
Measure: Assessment of changes in tidal volume during ECCO2R Time: Up to 72 hoursDescription: Assessment of changes in pH
Measure: Assessment of changes in pH during ECCO2R Time: Up to 72 hoursDescription: Assessment of changes in Positive End-Expiratory Pressure
Measure: Assessment of changes in Positive End-Expiratory Pressure during ECCO2R Time: Up to 72 hoursDescription: Adverse events directly related to ECCO2R are infection at the catheter site, hemorrhage at the cannulation site, air entry in the circuit.
Measure: Number of participants with adverse events directly related to ECCO2R Time: Up to 72 hoursDescription: Adverse events directly related to ECCO2R are clotting of the circuit.
Measure: Rate of technical adverse events related to ECCO2R Time: Up to 72 hoursDescription: Delta change in delta venous partial pressure of carbon dioxide before and after ECCO2R membrane
Measure: Delta change in venous partial pressure of carbon dioxide before and after ECCO2R membrane Time: Up to 72 hoursThis study will assess the feasibility of administering multiple doses of convalescent plasma (from people who have recovered form SARS-CoV-2) to Covid-19 positive patients in the Intensive Care Unit receiving mechanical ventilation. Donor plasma will not be obtained under this protocol, but all plasma used will follow FDA guidelines for Investigational COVID-19 Convalescent Plasma use. Patients may receive single or double plasma units infused on days 0, 3, and 6. This decision may be based on availability of blood plasma. The primary objective of this study is feasibility. Feasibility will be assessed based on the proportion of subjects who consent and receive at least one dose of convalescent plasma. The study will be declared 'feasible' if at least 80% of subjects who consent receive at least one dose. The secondary study endpoint is overall survival at day 60 after first dose of convalescent plasma. Respiratory status and overall clinical status will be reviewed during follow up on days 14, 28, and 60.
Description: Feasibility of administering convalescent plasma to patients in the ICU who are intubated and mechanically ventilated due to COVID-19-induced respiratory failure will be assessed based on the proportion of subjects who consent and receive at least one dose of CP. The study will be declared 'feasible' if at least 80% of subjects who consent receive at least one dose.
Measure: Proportion of subjects who consent to the study and receive at least one dose of convalescent plasma. Time: 60 daysDescription: Overall survival (days, until Day 60). This will be quantified as number of trial patients alive at Day 60 after first dose of CP / total number of patients who received at least one dose of CP.
Measure: Overall survival of patients in the ICU receiving at least once dose of convalescent plasma for Covid-19-induced respiratory failure. Time: 60 daysThe aim of the present study is to examine the inflammatory response in the pulmonary compartment and blood of critically ill patients admitted to the ICU with COVID-19.
Description: Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood
Measure: White blood cell counts Time: Day 0 (subsequent to study inclusion in the ICU)Description: Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood
Measure: White blood cell counts Time: Day 7Description: Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood
Measure: Lymphocyte populations Time: Day 0 (subsequent to study inclusion in the ICU)Description: Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood
Measure: Lymphocyte populations Time: Day 7Description: Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1)
Measure: Cytokines Time: Day 0 (subsequent to study inclusion in the ICU)Description: Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1)
Measure: Cytokines Time: Day 7Description: MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma
Measure: Lectin complement pathway Time: Day 0 (subsequent to study inclusion in the ICU)Description: MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma
Measure: Lectin complement pathway Time: Day 7Description: Growth of pathogenic microorganisms in body fluids (e.g. urine, blood, bronchoalveolar lavage fluid)
Measure: Microorganisms Time: Up to 12 weeksDescription: Respiratory filmarray PCR for testing for pathogens
Measure: Respiratory pathogens Time: Day 0 (subsequent to study inclusion in the ICU)Description: Respiratory filmarray PCR for testing for pathogens
Measure: Respiratory pathogens Time: Day 7Description: 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid
Measure: Ribosomal RNA in the airways Time: Day 0 (subsequent to study inclusion in the ICU)Description: 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid
Measure: Ribosomal RNA in the airways Time: Day 7Description: Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid
Measure: Levels of SARS-CoV-2 in the airways Time: Day 0 (subsequent to study inclusion in the ICU)Description: Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid
Measure: Levels of SARS-CoV-2 in the airways Time: Day 7Description: ICU mortality
Measure: Mortality Time: Up to 6 monthsDescription: In hospital mortality
Measure: Mortality II Time: Up to 6 monthsDescription: C-reactive protein, procalcitonin, ferritin
Measure: Blood markers of inflammation Time: Daily assessment in the ICU up to 12 weeksDescription: Platelets, creatinine, urea, sodium, potassium, D-dimer, lactate dehydrogenase, bilirubin, lactate
Measure: Blood markers of organ dysfunction Time: Daily assessment in the ICU up to 12 weeksDescription: Number of participants with unilateral infiltrates or bilateral infiltrates and/or air bronchogram
Measure: Infiltrates on conventional chest x-ray Time: Up to 12 weeksDuring Covid-19 pandemic many patients require mechanical ventilation due to disastrous impact of SARS-CoV-2 on lungs. In several countries there is a shortage of ICU beds and ventilators. Critically ill patients are treated outside ICUs. Doctors are facing ethical dilemmas who they should treat with ventilation, who should receive ventilator and who should but will not. In ICUs or step down units or in nursery homes there are also patients beyond hope treated - very often they are dependent on mechanical ventilation. Some attempts to invent a device that could replace complex machines in patients with anticipated poor outcome have been made. Ventil was used in clinical scenarios for separate lung ventilation with good effect. As a flow divider it has a potential to ventilate 2 patients at the same time. In the study Ventil will ventilate one patient and instead of the second there will be an artificial lung. Tidal volumes, minute ventilation, PEEP set and final will be checked. Ppeak, Pmean, Pplat, Cdyn, airway resistance, EtCO2, Sat O2, HR, SAP, DAP will be monitored every 2 hrs, as well as blood-gas analysis (every 8 hrs).
Description: Ventil will be removed from the patient-ventilator circiuit in case of episodes of desaturation <90% (in pts without COPD) without reversibel reason; need for FiO2 increase by 10%; need for switch to other than CMV mode of ventillation need for neuromucular blockade or for deepen sedation because of assynchrony between patient and venilator cummulation of CO2>45 mm Hg (in pts without COPD) not responding to the increase of minute ventilation for 30 minutes; if Pplat >30 cmH2O; in case of new haemodynamic disturbances that cannot be explaned by other reasons; in case of increase or decrease of BP by 20%; increase or decrease of HR by 20%; in case of occurence of clinically important heart rhythm disturbances
Measure: Number of cases in which it was necessary to stop using Ventil and to step- back to ventilation without this flow divider Time: 48 hoursIn the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure. Also due to the potential co-existing immunodysfunction in the context of SARS-CoV-2 infection patients will also receive trimethoprim/sulfamethoxazole as part of chemoprophylaxis.
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.
Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Measure: Rate of endotracheal intubation Time: 7 daysDescription: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.
Measure: Discontinuation rate of the treatment Time: 28 daysThe global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.
Description: Ideally, the PaO2/FiO2 will be measured with the patient in the same prone/supine position as in baseline, as change in positions may artificially reduce the improvement attributable to the study drug. However, given the pragmatic nature of the trial, the prone/supine position will be determined by the attending physician, in which case, we will use as an outcome the PaO2/FiO2 closest to the 48 hours obtained prior to the change in position as the outcome.
Measure: PaO2/FiO2 improvement from pre-to-post intervention Time: at 48 hours post randomizationDescription: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 (whatever is lower)
Measure: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 Time: at 48 hours post randomizationDescription: This score is based on seven clinical features (respiration rate, hypercapnic respiratory failure, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness) and determines the degree of illness of a patient and prompts critical care intervention.
Measure: National Early Warning Score 2 (NEWS2) Time: at 48 hours post randomizationDescription: The ordinal scale is an assessment of the clinical status 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. (combined items 7 and 8 as our study is limited to hospital).
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale Time: at 48 hours post randomizationDescription: 48 hour mortality for hospitalized patients
Measure: 48 hour in-hospital mortality Time: at 48 hours post randomizationDescription: 14 days mortality for hospitalized patients
Measure: 14 days in-hospital mortality Time: 14 days post randomizationDescription: 28 days mortality for hospitalized patients
Measure: 28 days in-hospital mortality Time: 28 days post randomizationDescription: ICU-free days will be calculated based on (28 - number of days spent in the ICU) formula
Measure: ICU-free days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: In-hospital coagulation-related events include bleeding, stroke, myocardial infarction and venous thromboembolism (VTE). In-hospital coagulation-related event-free (arterial and venous) days will be calculated based on (28 - number of days without coagulation-related event) formula.
Measure: In-hospital coagulation-related event-free (arterial and venous) days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: Ventilator-free days will be calculated based on (28 - number of days on mechanical ventilation) formula.
Measure: Ventilator-free days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: Calculated for patients who was on a mechanical ventilation any period of time during hospitalization. The extubation will be considered successful if no re-intubation occurred for more than 3 days have passed after the initial extubation.
Measure: Successful extubation Time: Day 4 after initial extubationDescription: Calculated for patients who was on paralytics at the time of randomization. The weaning will be considered successful if no paralytics were used for more than 3 days have passed after termination of paralytics.
Measure: Successful weaning from paralysis Time: Day 4 after initial termination of paralyticsDescription: Is counted for the patients who was alive at the time of discharge.
Measure: Survival to discharge Time: 28 days of hospital stay or until hospital discharge (whichever comes first)To characterize the ability of the D2000 Cartridge in combination with the Optia SPD Protocol to reduce the morbidity and mortality associated with SARS-CoV-2 infection in patients admitted to the ICU.
Description: Scale of 0-24 with a higher number indicating a worse outcome
Measure: Change in Sequential Organ Failure Assessment [SOFA] scores Time: Day 28The investigators hypothesize that those with respiratory failure due to COVID-19 will have different burdens of mental and physical disability than those with respiratory failure who do not have COVID-19. Detecting these potential differences will lay an important foundation for treating long term sequelae of respiratory failure in these two cohorts.
Description: SF-36 score
Measure: Quality of Life score Time: up to 12 months after dischargeDescription: Montreal Cognitive Assessment (MoCA) score
Measure: cognitive dysfunction Time: up to 12 months after dischargeDescription: (FSS-ICU)
Measure: Functional Status Score Time: up to 12 months after dischargeDescription: MRC neuromuscular Assessment
Measure: Physical Disability Time: up to 12 months after dischargeDescription: Impact Event Score
Measure: Psychological Sequelae Time: up to 12 months after dischargeDescription: hospital anxiety and depression scale
Measure: hospital anxiety and depression Time: up to 12 months after dischargeDescription: including ventilator associated pneumonia, GI hemorrhage, Deep Vein Thrombosis (DVT) /Pulmonary Embolus (PE), sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: hospitalization up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home
Measure: hospital discharge location Time: hospital discharge up to 6 weeksDescription: number of days admitted to the ICU
Measure: lCU length of stay Time: hospitalization up to 6 weeksDescription: number of days admitted to the hospital
Measure: hospital length of stay Time: hospitalization up to 6 weeksProspective observational study aimed at analyzing the incidence, clinical characteristics and outcomes of COVID-19 in LT in Spain.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic of coronavirus disease (COVID-19) that can lead to respiratory failure requiring oxygen therapy. Some patients develop acute respiratory distress syndrome (ARDS) and may die despite intensive care therapy. Currently it is unknown a) how fast patients recover after being discharged from hospital and b) what underlying predictors may influence recovery.
Description: European Quality of Life - 5 Dimensions - 5 Levels Instrument (EQ-5D-5L). Scoring: Index ranges from 1 to <0, with lower scores indicating more limitations.
Measure: Health-related quality-of-life Time: 3 monthsDescription: Hospital Axiety and Depression Score (HADS). Scoring: Scores range from 0 to 42, with higher scores indicating more anxiety or depression symptoms.
Measure: Anxiety and depression Time: 3 monthsDescription: COPD Assessment Test (CAT). Scoring: Scores range from 0-40, with higher scores indicating more symptoms due to respiratory limitations.
Measure: Symptom burden Time: 3 monthsDescription: Forced expiratory volume in one second (FEV1) in liters and percent predicted.
Measure: Spirometry Time: 1 monthDescription: Forced vital capacity (FVC) in liters and percent predicted.
Measure: Spirometry Time: 1 monthAcute respiratory distress syndrome (ARDS) is a major complication among patients with severe disease. In a report of 138 patients with COVID-19, 20% developed ARDS at a median of 8 days after the onset of symptoms, with 12.3% of patients requiring mechanical ventilation. Efficacious therapies are desperately needed. Supportive care combined with intermittent prone positioning may improve outcomes. Prone positioning (PP) of patients with severe ARDS (when combined with other lung-protective ventilation strategies) is associated with a significant mortality benefit. In addition, PP for >12 hours in severe ARDS is strongly recommended by clinical practice guidelines. The aim of this study is to compare the outcomes of prone positioning versus usual care positioning in non-intubated patients hospitalized for COVID-19.
This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).
Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment
Measure: P/F ratio Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.
Measure: A-a O2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Number of days on continuous positive end expiratory pressure (CPAP)
Measure: CPAP duration Time: From the first day of study drugs administration (T0) until day 7 post study drugs administrationDescription: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation
Measure: In-hospital change in intensity of the respiratory support Time: At baseline and 72 and 168 hours after treatment initiationDescription: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaCO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: HCO3- difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: Lactate difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Hb difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Plt difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)
Measure: Adverse effects Time: From the first day of study drugs administration until day 30 post study drugs administrationPatients with the acute respiratory distress syndrome (ARDS) have markedly varied clinical presentations. Main characteristics of mechanically ventilated ARDS caused by COVID-19, and adherence to lung-protective ventilation strategies are not well known.
Acute respiratory failure (ARF) is a common condition and a common reason for urgent medical consultation. Assessing the extent of respiratory impairment is important to improve the management of patients with ARF. When Acute respiratory failure is caused by pathology of the pulmonary parenchyma, quantification of pulmonary radiographic involvement may be a component of the initial assessment of severity. This radiographic quantification would only be usable in clinical routine if it can be automated and provide a real-time result. The objective of this work is to assess the feasibility of an automated technique for quantifying radiological lung damage in situations of known or potential ARF.
This is a protocol-driven observational study of lung ultrasound and focused echocardiography images obtained in the Emergency Department (ED) and Intensive Care Unit (ICU) settings as a part of existing standard of care. The objectives of this study are as follows: 1. To characterize various clinical and cardiopulmonary ultrasound findings and describe their relationship with the clinical course of patients with COVID-19 in the ED and ICU. 2. To describe, develop, and validate a prediction tool that can accurately predict the need for invasive mechanical ventilation (IMV) and acute respiratory failure in COVID-19 patients using clinical, laboratory, and ultrasound data.
Description: Number of patients requiring invasive mechanical ventilation and suffers from acute respiratory failure.
Measure: Patient requires invasive mechanical ventilation and suffers from acute respiratory failure. Time: 1 YearDescription: Number of patients that do not require hospitalization and is able to safely recover from COVID-19 at home.
Measure: Patient is discharged Time: 1 YearDescription: Number of patients that must be hospitalized to recover from COVID-19, but does not require invasive mechanical ventilation and may or may not suffer from some degree of acute respiratory failure.
Measure: Patient is hospitalized, but does not require mechanical ventilation through the duration of hospital stay. Time: 1 YearDescription: Any lung ultrasound findings including, but not limited to b-lines, a-lines, consolidations, pleural effusions and regularities. All of these findings are consolidated to a single score which will be the measure of the severity of lung ultrasound findings.
Measure: Lung ultrasound findings Time: 1 yearDescription: Any cardiac ultrasound findings including, but not limited to IVC status, pericardial effusions, LV EF (%), RV function. All of these findings are consolidated to a single score which will be the measure of the severity of cardiac ultrasound findings.
Measure: Cardiac ultrasound findings Time: 1 yearThe purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.
Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.
Measure: Ventilator-Free Days (VFD) Time: 28 daysDescription: Days spent in the ICU and hospital after time of enrollment
Measure: ICU and Hospital Length of Stay Time: 28 daysDescription: Incidence and time to intubation in days after the time of enrollment
Measure: Intubation Time: 28 daysDescription: Incidence of RRT after the time of enrollment
Measure: Renal Replacement Therapy (RRT) Time: 28 daysDescription: Death from any cause during after the time of enrollment
Measure: Mortality Time: 28 days, 90 daysDescription: Changes in Borg Dyspnea Score after time of enrollment
Measure: Dyspnea Time: 1 hourThe study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.
Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.
Measure: APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier) Time: up to Day 15Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
Measure: Serum C-reactive protein (CRP) levels Time: up to Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status over time Time: up to Day 29Description: Proportion of participants not requiring mechanical ventilation for survival.
Measure: Proportion of participants not requiring mechanical ventilation for survival. Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Proportion of participants with at least one-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29The study is a prospective, randomized, controlled investigation designed for comparison of two groups for the reduction of respiratory distress in a CoViD-19 population, using gammaCore Sapphire (nVNS) plus standard of care (active) vs. standard of care alone (SoC), the control group. The gammaCore® (nVNS) treatments will be used acutely and prophylactically. The active and control groups will be diseased and severity matched. The primary objective is to reduce initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Secondary objectives are to evaluate cytokine trends/prevent cytokine storms, evaluate supplemental oxygen requirements, decrease mortality of CoViD-19 patients and to delay the onset of mechanical ventilation.
Description: measure the change (in hours) between the control group and treatment group
Measure: change in initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first, assessed up to 3 monthsDescription: measure the changes in the serum/plasma concentrations of TH1 and TH2-type cytokines
Measure: evaluate cytokine trends Time: From the time of initial blood draw until the time of final blood draw, assessed up to date of mechanical ventilation, death, or discharge from hospital, whichever occurs first,assessed up to 3 monthsDescription: compare the difference in oxygen requirements (liters/min) between the control group and active group for patients admitted to the hospital for CoViD-19.
Measure: evaluate supplemental oxygen requirements Time: From the time of randomization, assessed up to time of mechanical ventilation, day of discharge or death, whichever occurs first,assessed up to 3 monthsDescription: measure the change (in hours) to death between control group and treatment group
Measure: decrease mortality of CoViD-19 patients Time: From the time or randomization until the date of death from any cause, assessed up to day of discharge or death,assessed up to 3 monthsDescription: measure the change (in hours) to time of mechanical ventilation between control group and treatment group
Measure: delay onset of ventilation Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first,assessed up to 3 monthsThe study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function
Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.
Measure: APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier) Time: Up to 15 daysDescription: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.
Measure: Serum C-reactive protein (CRP levels) Time: Up to 15 daysDescription: Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.
Measure: Ferritin levels Time: Up to 15 daysDescription: Proportion of participants without the need for invasive mechanical ventilation for survival.
Measure: Proportion of participants without the need for invasive mechanical ventilation Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Proportion of participants with at least one level improvement in clinical status Time: Day 15, Day 29Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status over time Time: Up to 15 daysThe study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Mean change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Median change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: mean change in 6-point ordinal scale change Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).Description: defined as independence from supplemental oxygen
Measure: Time since randomization until improvement in oxygenation Time: during hospital admission (up to 28 days)Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen
Measure: Number of days with hypoxia Time: during hospital admission (up to 28 days)Description: defined as 37.1°C or more
Measure: Number of days with fever Time: during hospital admission (up to 28 days)Description: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1 and day 6 Time: day 1, day 6 or on discharge, whichever is firstDescription: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1and day 15 (or on discharge, whichever is first) Time: day 1, day 15 or on discharge, whichever is firstDescription: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1 and day 28 (or on discharge, whichever is first) Time: day 1, day 28 or on discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first) Time: day 1, day 6 or on discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first) Time: day 1, day 15 or on discharge, whichever is firstDescription: NEWS2 score: 0 (best) - 24 (worse)
Measure: Mean change NEWS2 (National Early Warning) score between day 1 and day 6 Time: day 1, day 6 or on discharge, whichever is firstDescription: NEWS2 score: 0 (best) - 24 (worse)
Measure: Mean change NEWS2 (National Early Warning) score between day 1 and day 15 Time: day 1, day 15 or on discharge, whichever is firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call) Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: defined by Hs (Hemophagocytic Syndrome) score
Measure: incidence of secondary haemophagocytic lymphohistiocytosis in relation to serum D-dimers and complement C5a at randomization Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: criteria-defined ARDS (according to the American-European Consensus Conference (AECC) diagnostic criteria for ARDS: acute onset; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) of 200mmHg or less, regardless of positive end-expiratory pressure; bilateral infiltrates seen on frontal chest radiograph; and pulmonary artery wedge pressure of 18 mm Hg or less when measured, or no clinical evidence of left atrial hypertension)
Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome) in ventilated patients Time: during hospital admission (up to 28 days)Description: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1 and follow up 12-22 weeks Time: day 1, follow-up 12-22 weeksIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement Time: 72 hoursDescription: time to successful ECMO-explantation within 30 days after randomization
Measure: time to successful ECMO-explantation Time: 30 daysDescription: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization
Measure: Ventilator free days (VFD) Time: 30 daysDescription: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.
Measure: Time to extubation from ventilation and explantation from ECMO Time: 30 daysDescription: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.
Measure: Overall survival time Time: 30 daysDescription: Days on intensive care unit (ICU)
Measure: Days on intensive care unit (ICU) Time: 30 daysDescription: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h
Measure: Vasopressor dosage Time: 24, 48, 72 hoursDescription: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h
Measure: Fluid substitution and fluid balance Time: 24, 48, 72 hoursDescription: Serum lactate at 24, 48, 72 h
Measure: Serum lactate Time: 24, 48, 72 hoursDescription: Urine output at 24, 48, 72 h
Measure: Urine output Time: 24, 48, 72 hoursDescription: Willebrand factor at 24, 48, 72 h
Measure: Willebrand factor Time: 24, 48, 72 hoursDescription: d-dimers at 24, 48, 72 h
Measure: d-dimers Time: 24, 48, 72 hoursDescription: interleukin-6 levels at 24, 48, 72 h
Measure: interleukin-6 levels Time: 24, 48, 72 hoursDescription: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)
Measure: SOFA-Score Time: 24, 48, 72 hoursDescription: serious complications or malfunctions related to the CytoSorb device
Measure: serious adverse device effects Time: 30 daysDescription: unintended air in the ECMO system during operation of the device
Measure: adverse event of special interest: air in the ECMO system Time: 30 daysDescription: unintended blood-clotting in the ECMO system during operation of the device
Measure: adverse event of special interest: blood-clotting in the ECMO system Time: 30 daysDescription: major bleeding events
Measure: adverse event of special interest: bleeding complications Time: 30 daysNasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.
Description: values of ROX index during ICU stay
Measure: Changes in ROX index Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: percentage of patients requiring intubation
Measure: NHF failure Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of flow used with NHF
Measure: NHF flow Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of inspired fraction in oxygen used with NHF
Measure: NHF inspired fraction in oxygen Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of pulse oxymetry during NHF therapy
Measure: oxygenation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: respiratory rate during NHF therapy
Measure: respiratory status Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with intubation
Measure: prediction of intubation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with NHF success (no intubation required)
Measure: prediction of NHF success Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsCoronavirus disease 2019 (COVID-19) is a disease caused by a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The most characteristic symptom of patients with COVID-19 is respiratory distress, leading to inability to sustain spontaneous breathing. In addition, patients with COVID-19 have dyspnea and respiratory muscle fatigue. Therefore, it is necessary to use strategies that minimize the impact of COVID-19 on the respiratory muscles, accelerating the ventilatory weaning process and optimizing the functional capacity of the involved muscles. Over the past years, evidence has shown the effectivity of photobiomodulation therapy (PBMT) combined with static magnetic field (sMF) (PBMT/sMF) in delaying muscle fatigue, decrease in markers of inflammatory damage and oxidative stress of skeletal muscle. These effects result in an improvement in the functional capacity of the irradiated muscles by PBMT/sMF. However, do date, there is a lack of evidence regarding the effects of PBMT/sMF on the respiratory muscles. Therefore, the irradiation of PBMT/sMF may result in improvement in the functional capacity of respiratory muscles in patients with COVID-19, accelerating the ventilatory weaning process of the patients intubated due to respiratory failure. In addition, the irradiation of PBMT/sMF may induce the increase of anti-inflammatory mediators' activity in patients with COVID-19. Thus, the aim of this project is to investigate the effects of PBMT/sMF on respiratory muscles of patients admitted to the Intensive Care Unit (ICU) with COVID-19 using invasive mechanical ventilation.
Description: Number of days hospitalized in the ICU until discharge or death.
Measure: Time until discharge Time: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days.Description: Rate of how many people survived and were discharged and how many died.
Measure: Survival rate Time: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 20 days.Description: Diaphragm thickness will be measured by ultrasound.
Measure: Diaphragm muscle function Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: Platelet count will be measured by blood test.
Measure: Platelet count Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: Leukogram will be measured by blood test.
Measure: Leukogram Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: Erythrogram will be measured by blood test.
Measure: Erythrogram Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: C-reactive protein will be measured by blood test.
Measure: C-reactive protein Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: D-dimer will be measured by blood test.
Measure: D-dimer Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: Immunoglobulin G will be measured by blood test.
Measure: Immunoglobulin G Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: Immunoglobulin M will be measured by blood test.
Measure: Immunoglobulin M Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: The levels of PEEP will be measured using a mechanical ventilator.
Measure: Levels of positive end-expiratory pressure (PEEP) Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: The levels of FiO2 will be measured using a mechanical ventilator.
Measure: Fraction of inspired oxygen (FiO2) Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: PO2 will be measured by arterial blood gas analysis.
Measure: Arterial partial pressure of oxygen (PO2) Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Description: PO2/FiO2 ratio will be measured by arterial blood gas analysis.
Measure: Arterial partial pressure of oxygen (PO2)/Fraction of inspired oxygen (FiO2) ratio Time: 10 days after randomization and in the last test before discharge or death from any cause, whichever came first, assessed up to 20 days.Ophthalmologic damages secondary to COVID-19 coronavirus infection are little described. The ocular involvement is probably multiple, ranging from pathologies of the anterior segment such as conjunctivitis and anterior uveitis to disorders that threaten vision such as retinitis or optic neuropathy. On the other hand, in addition to this impairment, when patients are hospitalized for acute respiratory failure, complications related to possible resuscitation, medication prescriptions, positioning and oxygenation. COVID-19 itself, has several components: - An apoptotic action of the viral attack which will generate cellular destruction, whether pulmonary, cardiac or renal or maybe ocular - A secondary autoimmune action with the development of major vascular inflammation, possibly reaching the retinal, choroidal, and optic nerve vessels. A secondary "hyper" inflammatory syndrome with flashing hypercytokinemia and multi-organ decompensation is described in 3,7% to 4 ,3% of severe cases. - A thromboembolic action
Description: Multimodal ophthalmologic imaging
Measure: Description of the ophthalmological problems observed Time: 6 months after discharge of hospitalizationAim. The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Beside the prescription of some promising drugs as chloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab), in our patients with mild to moderate pneumonia due to SARS-CoV-2 we planned a randomize study to evaluate, respect the best available therapy (BAT), the use of autohemotherapy treatement with an oxygen/ozone (O3) gaseous mixture as adjuvant therapy. Design. Multicentric, randomized study. Participants. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU - Società Italiana di Medicina di Emergenza-Urgenza) and patients that meet criteria of phenotypes 2 to 4 were treat with best available therapy (BAT), and randomized to receive or not O3-autohemotherapy. Main outcome measures. The end-point were the time of respiratory improvement and earlier weaning from oxygen support: these parameters were included in the SIMEU clinical phenotypes classification.
Description: Evaluation of ABG paramethers the day after the last blood ozonization procedure (Day 3)
Measure: Time of respiratory improvement and earlier weaning from oxygen support Time: 3 daysDescription: Evaluation of ABG paramethers the one week after the last blood ozonization procedure (Day 10)
Measure: The time of respiratory improvement and earlier weaning from oxygen support Time: 10 daysDescription: Asse the lenghth of hospital stay in the two arms
Measure: Assessment of the length of hospitalization Time: up to 90 daysDescription: Asse the lenghth of ICU stay in the two arms
Measure: Assessment of the length of Intensive Care Unit (ICU) stay Time: up to 90 daysDescription: improving, worsening or stability of the chest imaging (chest CT, Chest XR and/or Point-of-Care Ultrasound) finding in the two arms
Measure: Improvment in chest imaging finding Time: 10 daysDescription: Evaluation of plasmatic cytochine (IL-6, lymphocyte typing for CD4, CD3, CD8, HLA-DR, CD45) response in the two arms
Measure: Improvment in cytokine release syndrome Time: 10 daysA randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Description: Alive and free of invasive mechanical ventilation
Measure: Proportion of participants who are alive and free of invasive mechanical ventilation Time: Through Day 28Description: Time to all-cause mortality
Measure: All-cause mortality Time: Through Day 28Prone position (PP) has been proved to be effective in severe ARDS patients. On the other hand, High flow nasal cannula (HFNC) may prevent intubation in hypoxemic Acute respiratory failure (ARF) patients. Our hypothesis is that the combination of PP and HFNC in patients with COVID19 induced ARDS may decrease the need of mechanical ventilation. Primary outcome: Therapeutic failure within 28 days of randomization (death or intubation). Secondary outcomes: to analyze PP feasibility and safety in HFNC patients and to analyze effectiveness in terms of oxygenation. Methods: multicentric randomized study including patients with COVID19 induced ARDS supported with HFNC. Experimental group will received HFNC and PP whereas observation group will received standard care. Optimization of non-invasive respiratory management of COVID19 induced ARDS patients may decrease the need of invasive mechanical ventilation and subsequently ICU and hospital length of stay.
Description: Therapeutic failure: death or intubation
Measure: Therapeutic failure death or intubation Time: 28 days within randomizationDescription: Comfort measurement using a visual-analog scale. Presence of complications related with prone position and the use of high-flow nasal cannula: Skin ulcers. Intravascular lines displacement HFNC related events (hot air feeling, nasal lesions)
Measure: Feasibility and safety of prone position in HFNC patients Time: 28 days within randomizationDescription: Evolution of the oxygenation (SpO2/FiO2) in prone position. Efficacy Length of HFNC therapy Length of ICU stay Length of mechanical ventilation (in those who require intubation) ICU and hospital mortality
Measure: Efficacy of prone position in HFNC patients Time: 28 days within randomizationThe aim of the present study is to examine whether cerebral oxygenation could be a more useful parameter than peripheral oxygen saturation to guide clinical titration of permissive hypoxemia in COVID-19 ARDS patients
Description: Cardiovascular and pulmonary optimization: Step 0 = Baseline, Step 1 = Derecruitment, Step 2 = Recruitment, Step 3 = Norepinephrine challenge, Step 4 = FiO2 increase, Step 5 = FiO2 decrease, Step 6 = Baseline 2
Measure: Changes in cerebral oxygenation (ScO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in peripheral oxygen saturation (SatO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in systolic arterial pressure (SAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in diastolic arterial pressure (DAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in mean arterial pressure (MAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in heart rate (HR) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in stroke volume (SV) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in cardiac output (CO) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in systemic vascular resistance (SVR) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in peripheral perfussion index (PPI) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in pH during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in PaO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in PaCO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in arterial saturation (SaO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in PvO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in PvCO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in mixed venous saturation (SvO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in lacatate during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in hemoglobine concentration (Hb) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Changes in muscular oxygenation (SmO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and peripheral oxygen saturation (SatO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and systemic arterial pressure (SAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and diastolic arterial pressure (DAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and mean arterial pressure (MAP) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and stroke volume (SV) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and heart rate (HR) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and cardiac output (CO) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and systemic vascular resistance (SVR) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and peripheral perfussion index (PPI) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and pH during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and PaO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and PaCO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and arterial saturation (SaO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and PvO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and PvCO2 during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and mixed venous saturation (SvO2) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and lactate during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and hemoglobine concentration (Hb) during cardiovascular and pulmonary optimization Time: 1 hourDescription: Cardiovascular and pulmonary optimization as described above
Measure: Association between cerebral oxygenation (ScO2) and muscular oxygenation (SmO2) during cardiovascular and pulmonary optimization Time: 1 hourA phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).
Description: 7-point ordinal scale is defined as 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 patients reporting each severity rating on a 7-point ordinal scale Time: 28-day treatment periodDescription: Nasopharyngeal sample and/or in blood
Measure: SARS-CoV-2 viral load Time: at each study visit during the 28-day treatment periodThe novel SARS-CoV-2 virus has quickly spread worldwide, with substantial morbidity and mortality. There is very limited understanding of the short- and longer-term inflammatory/immunological and clinical course. However, the investigators expect survivors from severe COVID-19 to experience persistent functional impairments, as demonstrated in prior studies of patients with acute respiratory distress syndrome (ARDS) and other acute viral illnesses. Notably, however, few studies have ever investigated the biologic mechanisms underlying these functional impairments. Understanding these features of COVID-19 will improve the ability to design acute therapies and recovery-focused interventions. To address these knowledge gaps, the investigators propose a two-center, 225 patient longitudinal prospective cohort study of hospitalized COVID-19 patients with acute respiratory failure. Researchers will perform an in-depth evaluation of inflammatory/immunological biomarkers, and physical, pulmonary, and neuropsychological clinical outcomes during hospitalization, and over 3-, 6-, and 12-month follow-up.
Description: Exercise capacity
Measure: Six minute walk distance (6MWD) Time: 3 months after hospital admissionDescription: Exercise capacity
Measure: Six minute walk distance (6MWD) Time: 6 months, 12 months after hospital admissionDescription: Symptoms of anxiety and depression. Both anxiety and depression subscales are scored from 0-21, with higher scores indicating more symptoms.
Measure: Hospital Anxiety and Depression Scale (HADS) Time: 3 months, 6 months, 12 months after hospital admissionDescription: Health-related quality of life. The EQ-5D-5L is scored from 0-100, with a higher score indicating better health status.
Measure: EuroQol Group standardized measure of health status (EQ-5D-5L) Time: 3 months, 6 months, 12 months after hospital admissionDescription: Mental and Cognitive Functioning. The MoCA-BLIND is scored from 1-22, with higher scores indicating better cognitive function.
Measure: MoCA-BLIND Time: 3 months, 6 months, 12 months after hospital admissionDescription: Health Care Utilization
Measure: Health Care Utilization Survey (HUS) Time: 3 months, 6 months, 12 months after hospital admissionDescription: Mortality
Measure: Death Time: 3 months, 6 months, 12 months after hospital admissionDescription: The maximum volume of gas expired when the patient exhales as forcefully and rapidly as possible after a maximal inspiration. Obtained by spirometry.
Measure: Forced vital capacity (FVC) Time: 3 months, 6 months, 12 months after hospital admissionDescription: Measure of the volume expired over the first second of an FVC maneuver. Obtained by spirometry
Measure: Forced expiratory volume in 1 second (FEV1) Time: 3 months, 6 months, 12 months after hospital admissionDescription: Gait speed
Measure: 4-meter timed walk Time: 3 months, 6 months, 12 months after hospital admissionDescription: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.
Measure: Peripheral blood mononuclear cell type: CD4+ T cells (#cells/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.
Measure: Peripheral blood mononuclear cell type: CD8+ T cells (#cells/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.
Measure: Peripheral blood mononuclear cell type: B cells (#cells/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.
Measure: Peripheral blood mononuclear cell type: NK cells (#cells/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.
Measure: Peripheral blood mononuclear cell type: monocytes (#cells/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: C-Reactive Protein (CRP) (mg/l) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Interleukin 6 (IL-6) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Interleukin 8 (IL-8) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Interferon gamma (IFNg) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Interferon alpha (IFNa) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Tumor necrosis factor alpha (TNFa) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionDescription: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.
Measure: Circulating markers of inflammation: Interleukin 1 beta (IL-1b) (pg/ml) Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admissionProne positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.
Description: Total time spent in prone position, as recorded by nursing or respiratory therapists
Measure: Time in prone position Time: Up to 28 days post randomizationDescription: Daily evolution of oxygenation
Measure: Oxygenation (SpO2/FiO2 ratio) Time: Until HFNC weaning, or up to 14 days after randomization, whichever is firstWe aim to investigate whether the use of Continuous Positive Airway Pressure using a Helmet device (Helmet CPAP) will increase the number of days alive and free of ventilator within 28 days compared to the use of a High Flow Nasal Cannula (HFNC) in patients admitted to Helsingborg Hospital, Sweden, suffering from COVID-19 and an acute hypoxic respiratory failure.
Description: Number of days alive and free of mechanical ventilation within 28 days. Patients who die within 28 days will be counted as 0 VFD. Time in ventilator will be counted in hours and rounded to whole days.
Measure: Ventilator-Free Days (VFD) Time: 28 daysDescription: Peripheral oxygen saturation divided by fraction of inspired oxygen
Measure: SpO2/FiO2-ratio Time: 1 hour after randomisationDescription: Visual scale (1-10)
Measure: Patient comfort Time: 24 hours after randomisationDescription: Min 0, Max 1
Measure: Frequency of endotracheal intubation Time: 28 daysDescription: Defined as pCO2 > 6 kPa in a venous blood gas. Min 0, Max ∞
Measure: Frequency of carbon dioxide rebreathing Time: 28 daysDescription: All-cause mortality. (180 days endpoint not in primary publication)
Measure: Days alive within Time: 28 days and 180 daysThis study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.
Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm
Measure: Reduction in the dependency on oxygen supplementation Time: within day 14 of treatmentDescription: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Proportion of responders (using the WHO 7-point ordinal scale) Time: Day 7, 14, and 28Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Time to response (using the WHO 7-point ordinal scale) Time: Within day 28 of interventionDescription: Proportion of patients with at least two-point improvement in clinical status
Measure: Proportion of improving patients (using the WHO 7-point ordinal scale) Time: At day 7, 14, and 28Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner
Measure: Time to resolution of fever Time: Within day 28 of interventionDescription: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of interventionDescription: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)
Measure: Proportion of patient requiring mechanical ventilation/deaths Time: Within day 14 of interventionDescription: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)
Measure: Change in biochemical markers Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)
Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2) Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.
Measure: Variations in radiological findings Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs
Measure: Safety of mavrilimumab in patients with severe COVID-19-pneumonia Time: By day 84Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg
Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity Time: Within day 28 of interventionDescription: Changes in exploratory biomarkers: Inflammatory biomarkers (i.e. IL-6, IL-1RA, TNF-alpha, CBC and differential) Levels of antibodies to SARS- CoV-2 / SARS-Cov-2 positivity by PCR Levels of anti-drug antibiodies (ADA)
Measure: Changes in exploratory biomarkers Time: By day 84The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: Day 14Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: Day 28Contagious disease outbreaks, such as the coronavirus disease 2019 (COVID-19) outbreak, and associated restrictions to prevent spread can lead to negative psychological outcomes, including loneliness, depression, and anxiety, particularly in vulnerable populations at risk due to existing medical conditions. To date, no randomized controlled trials have tested interventions to reduce mental health consequences of contagious disease outbreaks. Systemic sclerosis (SSc; scleroderma) is a rare, chronic, autoimmune disease characterized by vasculopathy and excessive collagen production. Systemic Sclerosis can affect multiple organ systems, including the skin, lungs, gastrointestinal tract, and heart. Many people with scleroderma are at risk of serious complications from COVID-19 if infected due to lung involvement (> 40% have interstitial lung disease) and common use of immunosuppressant drugs. The objective of The Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate a videoconference-based intervention designed to improve symptoms of anxiety and other mental health outcomes among individuals with systemic sclerosis at risk of poor mental health during the COVID-19 pandemic. The trial is a pragmatic randomized controlled trial that will be conducted using an existing cohort of systemic sclerosis patients. We will use a partially nested design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support.
Description: The PROMIS Anxiety 4a v1.0 is a 4 item scale that asks participants, in the past 7 days, how often: (1) "I felt fearful"; (2) "I found it hard to focus on anything other than my anxiety"; (3) "My worries overwhelmed me"; and (4) "I felt uneasy". Items are scored on a 5-point scale (range 1-5), and response options include "never", "rarely", "sometimes", "often", and "always". Higher scores represent more anxiety. PROMIS Anxiety 4a v1.0 has been validated in SSc.
Measure: Anxiety: Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a v1.0 Time: 4-weeks post-randomizationDescription: PHQ-8 items measure depressive symptoms over the last 2 weeks on a 4-point scale, ranging from 0 (not at all) to 3 (nearly every day) with higher scores (range 0 to 24) indicating more depressive symptoms. The PHQ-8 performs equivalently to the PHQ-9, which has been shown to be a valid measure of depressive symptoms in patients with scleroderma.
Measure: Depression symptoms: Patient Health Questionnaire (PHQ-8) Time: 4-weeks post-randomizationDescription: The 10-item PSS measures the degree that respondents appraise their lives as stressful; items are designed to reflect the degree that they find their life circumstances in the last 4 weeks to be unpredictable, uncontrollable, or overloaded. Items are scored on a 5-point scale from 0 (never) to 4 (very often). Total scores (range 0 to 40) are computed by summing individual items scores, and higher scores reflect greater perceived stress. The PSS has been validated in many medical and non-medical populations.
Measure: Stress: Perceived Stress Scale (PSS) Time: 4-weeks post-randomizationDescription: The 6-item ULS-6 is a short version of the 20-item ULS, which is designed to assess subjective feelings of loneliness and social isolation. Respondents indicate the degree to which feelings described in each item apply to them. Items are scored on a 4-point scale from 0 (never) to 3 (often); total scores range from 0 to 18.
Measure: Loneliness: University of California, Los Angeles (UCLA) Loneliness Scale (ULS-6) Time: 4-weeks post-randomizationDescription: The full MSBS is a 29-item measure of state boredom with items on five factors that load onto a single higher-order factor. The 8-item MSBS is a short version with scores that correlate very closely to scores from the full MSBS (r = 0.96) Item responses are on a 7-point Likert-type scale from 1 (strongly disagree) to 7 (strongly agree) and assess the degree to which each item reflects the respondant's experience currently. Total scores range from 8 to 56 with higher scores reflecting greater boredom.
Measure: Boredom: Multidimensional State Boredom Scale (MSBS-8) Time: 4-weeks post-randomizationDescription: The 4-item IPAQ-E is a short-form version of the full IPAQ designed to assess physical activity over the last week, including time spent sitting, walking, and in moderate and vigorous physical activity. Compared to other short-form versions of the IPAQ, the IPAQ-E has examples of exercise specific to older adults.
Measure: Physical activity: International Physical Activity Questionnaire - modified for the elderly (IPAQ-E) Time: 4-weeks post-randomizationDescription: Frequency of social interactions with others inside and outside of the home will be measured with 4 separate items, including (1) On a typical day in the last week, how many times did you have a social conversation over the phone or a videoconferencing platform with one person? (response = number of times); (2) On a typical day in the last week, how many times did you have a social conversation over a videoconferencing platform with multiple people at the same time? (response = number of times); (3) In the last 7 days, on a typical day, how long did you spend enjoying conversations with other individuals in the home? (response = time); (4) In the last 7 days, on a typical day, how long did you spend enjoying activities with other individuals in the home? (response = time).
Measure: Frequency of social interactions Time: 4-weeks post-randomizationDescription: Adverse Effects will be assessed by ongoing monitoring during the trial and by asking participants post-intervention to describe any adverse experiences or outcomes that may have occurred.
Measure: Adverse Effects Time: 4-weeks post-randomization