Name (Synonyms) | Correlation | |
---|---|---|
drug2620 | VPM1002 Wiki | 0.24 |
drug1548 | NA-831and Dexamethasone Wiki | 0.21 |
drug303 | BNT162a1 Wiki | 0.21 |
drug1647 | Normobaric oxygen therapy Wiki | 0.21 |
drug2345 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki | 0.21 |
drug1116 | Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Wiki | 0.21 |
drug700 | DAS181 OL Wiki | 0.21 |
drug2346 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki | 0.21 |
drug1565 | NaCl Solution Wiki | 0.21 |
drug306 | BNT162c2 Wiki | 0.21 |
drug270 | Azithromycin and hydroxychloroquine Wiki | 0.21 |
drug1571 | Naso pharyngeal swab Wiki | 0.21 |
drug1096 | Hydroxychloroquine - Daily dosing Wiki | 0.21 |
drug1137 | Hyperbaric oxygen therapy Wiki | 0.21 |
drug898 | Extended sampling and procedures Wiki | 0.21 |
drug2344 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki | 0.21 |
drug1440 | Matched Placebo Hydroxychloroquine Wiki | 0.21 |
drug2699 | Women receiving extra remembering by healthcare Wiki | 0.21 |
drug1547 | NA-831 and Atazanavir Wiki | 0.21 |
drug3035 | trimethoprim/sulfamethoxazole Wiki | 0.21 |
drug1337 | Levamisole and isoprinosine Wiki | 0.21 |
drug235 | Atazanavir and Dexamethasone Wiki | 0.21 |
drug2347 | Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki | 0.21 |
drug1079 | Human milk donors Wiki | 0.21 |
drug1605 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.21 |
drug986 | Gam-COVID-Vac Lyo Wiki | 0.21 |
drug794 | Drug: NA-831 Wiki | 0.21 |
drug505 | CYNK-001 Wiki | 0.21 |
drug1993 | Quick Defense Wiki | 0.21 |
drug1166 | Icosapent ethyl Wiki | 0.21 |
drug490 | COVSurf Drug Delivery System Wiki | 0.21 |
drug2477 | Testing Sensitivity for SARS-CoV-2 Virus in Symptomatic Individuals Wiki | 0.21 |
drug899 | Extra blood sample Wiki | 0.21 |
drug699 | DAS181 COVID-19 Wiki | 0.21 |
drug1367 | Lopinavir/ Ritonavir Oral Tablet Wiki | 0.21 |
drug1097 | Hydroxychloroquine - Weekly Dosing Wiki | 0.15 |
drug305 | BNT162b2 Wiki | 0.15 |
drug304 | BNT162b1 Wiki | 0.15 |
drug1115 | Hydroxychloroquine Sulfate Tablets Wiki | 0.15 |
drug53 | ACE inhibitor Wiki | 0.12 |
drug923 | Favipiravir Wiki | 0.10 |
drug1706 | Oseltamivir Wiki | 0.09 |
drug698 | DAS181 Wiki | 0.09 |
drug1822 | Placebo Wiki | 0.08 |
drug159 | Anakinra Wiki | 0.08 |
drug1860 | Placebos Wiki | 0.05 |
drug1086 | Hydroxychloroquine Wiki | 0.04 |
drug2319 | Standard of Care Wiki | 0.04 |
Name (Synonyms) | Correlation | |
---|---|---|
D012141 | Respiratory Tract Infections NIH | 1.00 |
D030341 | Nidovirales Infections NIH | 0.21 |
D012327 | RNA Virus Infections NIH | 0.21 |
D003141 | Communicable Diseases NIH | 0.18 |
D007239 | Infection NIH | 0.17 |
D003139 | Common Cold NIH | 0.15 |
D014777 | Virus Diseases NIH | 0.13 |
D018184 | Paramyxoviridae Infections NIH | 0.12 |
D003333 | Coronaviridae Infections NIH | 0.10 |
D012140 | Respiratory Tract Diseases NIH | 0.10 |
D007154 | Immune System Diseases NIH | 0.09 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.09 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.07 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.07 |
D008173 | Lung Diseases, Obstructive NIH | 0.07 |
D007251 | Influenza, Human NIH | 0.06 |
D018352 | Coronavirus Infections NIH | 0.06 |
D008171 | Lung Diseases, NIH | 0.05 |
D000860 | Hypoxia NIH | 0.05 |
D011014 | Pneumonia NIH | 0.04 |
D011024 | Pneumonia, Viral NIH | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0010444 | Pulmonary insufficiency HPO | 0.09 |
HP:0006510 | Chronic pulmonary obstruction HPO | 0.07 |
HP:0006536 | Pulmonary obstruction HPO | 0.07 |
HP:0002088 | Abnormal lung morphology HPO | 0.05 |
HP:0012418 | Hypoxemia HPO | 0.05 |
HP:0002090 | Pneumonia HPO | 0.04 |
There are 23 clinical trials
Currently, there is no treatment for children less than one year of age with influenza related lower respiratory tract infection that is either considered standard or registered in any country. This dismal scenario exists even though influenza related LRTI is a significant illness causing morbidity and mortality, especially in children less than 6 months of age. Avian influenza has been reported rarely in children less than one. There are no data in Vietnam and very few data in Thailand on the burden of influenza in children less than one. This young age group suffers high mortality. Oseltamivir may be beneficial in such children. This is basis of this trial.
Description: Viral clearance on Day 5 (human influenza) on a throat swab, assessed by RT PCR. Viral clearance on Day 10 (avian influenza) on a throat swab, assessed by RT PCR.
Measure: Viral clearance Time: 5-10 daysDescription: • Cmax, Tmax, AUC, apparent volume of distribution, clearance, terminal elimination half-life
Measure: Pharmacokinetics of Oseltamivir Time: Day 0 and Day 9Description: Time to viral clearance on a throat swab, assessed by RT PCR. The time to no detectable influenza virus by culture for the throat swab. Change in viral load (log10 copies/mL) over time for all virological samples (lower limit of detection: 1000 copies/mL) Viral susceptibility of cultured influenza virus to antiviral drugs at baseline and post treatment, assessed by genotypical and phenotypical analyses
Measure: Viral end points Time: 5-10 daysDescription: Time to fever clearance In hospital mortality and mortality by follow up Time to death Time to trans cutaneous O2 saturation of ≥ 95% on room air Clinical course: pneumothorax, encephalitis/encephalopathy Number of days in hospital Number of days ventilated
Measure: Clinical Efficacy Endpoints Time: 5-10 daysDescription: Documented serious adverse events (SAEs) and relationships to oseltamivir AEs leading to drug withdrawal Grade 3 & 4 clinical and laboratory AEs that are probably or definitely related to oseltamivir Skin rashes of any grade Changes in haematological and biochemical parameters over time
Measure: Safety Endpoints Time: 5-10 daysThe primary objective of this study is to evaluate the effectiveness of ingesting an alkylamide-rich echinacea root product (Quick Defense, Gaia Herbs) for 2 days immediately following each onset of acute respiratory illness (ARI) symptomatology during a 12-week period in the winter and early spring in women. Hypothesis: Subjects randomized to Quick Defense compared to placebo over a 12-week period will experience reduced ARI symptomatology, both acutely during each ARI episode and collectively over the entire 12-week study period.
Description: The Wisconsin Upper Respiratory Symptom Survey (WURSS-24) will be used to assess common cold illness severity and symptoms (see attached questionnaire). Subjects will fill in the one-page WURSS-24 at the end of each day during the 12-week monitoring period. This 12-week period will cover the winter and early spring period of 2014. From the responses recorded during the 84-day study, an ARI severity score will be calculated by summing the daily ARI global severity score (0=not sick, 1=very mild ARI to 7=severe). The ARI symptom score for the 84-day period will be calculated by summing all 10 symptom scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). In similar fashion, the ARI function ability score for the 84-day period will be calculated by summing all 9 function scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). Separate scores will be calculated comparing groups for each illness episode recorded by the subjects.
Measure: Common cold symptoms Time: 12-weeksThe objective of this project is to study the prevalence of viruses and bacteria responsible for transmissible acute respiratory infections in the respiratory tract of pilgrims returning from the trip. The patients included, will be the consultant pilgrims to the traveler health center, and before leaving for Hajj. Based on the results obtained in previous studies, it is estimated that 200 pilgrims will be included each year, 600 in total (inclusion period of 3 years). Respiratory secretions are then collected by nasal swab and throat (swab) prior to departure for the hajj. In return, patients will be reconvened systematic consultation to record medical events potentially encountered during the trip, and it will again be performed the same nasal swabs and throat. It will then be performed on these samples' return from hajj "molecular detection (PCR and RT-PCR) of 35 viruses and bacteria respiratory tropism: influenza (3), RSV (2), metapneumovirus (1), Coronavirus (4), Parainfluenzavirus (4), enteroviruses (4), rhinovirus (1), adenovirus (6) bocavirus, polyomavirus (2), pneumococcus, Bordetella pertussis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Coxiella burnetii. Samples "return of hajj" positive should be cultured for the isolation of the strain. For patients positive return, it will be done further research of these 35 viruses and bacteria on samples "start of hajj," the same method described above. In addition to this systematic consultation, and if symptoms return, the pilgrims will be seen in consultation for a diagnosis evaluation and therapeutic management. This study will shed light on the acquisition of microorganisms respiratory tropism during the stay and on the potential risks associated with the circulation of these pathogens after the trip.
The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical community acquired pneumonia. Specific objectives: - To assess the diagnostic accuracy of MxA for viral CAP (sub-study I) - To study etiologies in children with CAP (sub-study II) - To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III) - To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV) - To assess long-term complications in children with CAP (sub-study V The study takes place at Sachs' Children and Youth hospital in Stockholm.
Description: Clinically relevant difference in MxA-levels between cases with viral and bacterial clinical CAP
Measure: MxA - cases with viral and bacterial clinical CAP Time: 2021Description: Clinically relevant difference in MxA-levels between cases with viral clinical CAP and controls
Measure: Mxa viral clinical CAP and controls Time: 2021Description: Proportion of respiratory pathogens in cases and controls, using real time PCR
Measure: PCR - respiratory pathogens in cases and controls Time: 2020Description: Sensitivity and specificity for different respiratory viruses with MariPOC® Respi as compared to real-time PCR
Measure: Sensitivity and specificity - MariPOC Time: 2021Description: Sensitivity and specificity for different respiratory viruses with a novel PCR-based point-of-care test as compared to PCR
Measure: Sensitivity and specificity a novel PCR-based point-of-care test Time: 2021Description: Difference in asthma prevalence between cases and controls and difference in number of hospital-requiring respiratory infections between cases and controls after 3, 7 and 10 years
Measure: Difference asthma prevalence and number of hospital-requiring respiratory infections - cases and controls, Time: 2027Description: Clinically relevant difference in MxA-levels comparing cases with viral clinical CAP with cases with atypical and mixed viral-bacterial clinical CAP as well as with controls with and without presence of respiratory viruses by PCR
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Clinically relevant differences in MxA-levels in cases with regard to specific respiratory agents
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Sensitivity and specificity for MxA in identifying viral clinical CAP
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Sensitivity and specificity for identifying viral and bacterial infection respectively for CRP, PCT and combination test of CRP, PCT and MxA
Measure: Specific assessment of MxA as a clinical biomarker Time: 2021Description: Difference in CRP and PCT between children with viral, bacterial, atypical bacterial and mixed viral-bacterial infection
Measure: Assessment of PCT and CRP as clinical biomarkers Time: 2021Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases with viral, bacterial, atypical bacterial and mixed viral-bacterial infection
Measure: Descriptive statistics of study cohort with regard to etiologic agent Time: 2020Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases who tested positive for respiratory virus by MariPOC® Respi as compared to those with a negative test
Measure: Evaluation of MariPOC® Respi in a clinical setting Time: 2022Description: Number of hospital-requiring respiratory infections in cases and controls
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in asthma prevalence between cases with viral and bacterial clinical CAP as compared to an estimate of the prevalence in the general population
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in proportion of hospital-requiring respiratory infections between cases with viral, bacterial, atypical and mixed viral-bacterial infection
Measure: Assessment of long-term outcomes of children with CAP Time: 2027Description: Difference in MxA-levels between PCR+/MariPOC® Respi+ and PCR+/MariPOC® Respi- study subjects.
Measure: Evaluation of MariPOC® Respi Time: 2022Description: Estimation of etiology of cases using two levels of certainty (definitive as well as probable definition).
Measure: Etiology of cases in TREND study Time: 2020Non 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 26This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.
Description: Removal of all oxygen support (with stable SpO2)
Measure: Percent of subjects who Return to Room Air (RTRA) (main study) Time: by Day 28Corona virus is known as covid 19 And is transmitted through droplet infection
Description: The number of pregnant women who have awareness about the disease
Measure: The number of pregnant women who know the exact symptoms of the disease Time: Within one monthOperational project to compare clinician collected nasopharyngeal (NP) samples to patient-obtained tongue, nasal and mid-turbinate (MT) samples in the detection of SARS-CoV-2 in an outpatient clinic setting
Description: compare clinician collected nasopharyngeal (NP) samples to patient-obtained tongue, nasal and mid-turbinate (MT) samples in the detection of SARS-CoV-2 in an outpatient clinic setting
Measure: Accuracy of patient administered tests Time: 2 weeksThe study use UK based linked electronic health records from the Clinical Research Datalink (CALIBER) of 5.6 million individuals to conduct a matched case-control study to investigate the incidence of influenza in individuals prescribed ACEI compared to those not prescribed ACEI.
An open access study that will define and collect digital measures of coughing in multiple populations and public spaces using various means of audio data collection.
Description: Size of collected audio dataset measured as number of collected cough sounds, targeting ≥10,000 identified coughs.
Measure: Dataset size Time: 14 daysDescription: Identification of cough sounds by the existing mathematical model with ≥ 99% specificity and ≥ 60% sensitivity
Measure: Cough sound identification Time: 14 daysDescription: Increase in the sensitivity of the mathematical model to cough sounds to ≥ 70% while retaining the specificity of ≥ 99%
Measure: Improvement of the existing model Time: 14 daysDescription: Determination of the level of acceptance and satisfaction of the solution by patients by means of a Standard Usability Questionnaire to provide feedback. The score ranges from 10 to 50, higher score indicating a better usability.
Measure: Evaluate the usability of the application Time: 14 daysORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)
Measure: COVID Ordinal Outcomes Scale on Day 15 Time: assessed on study day 15Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 15 Time: assessed on study day 15Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 29 Time: assessed on study day 29Description: We will determine the COVID Ordinal Scale for all patients on study day 3
Measure: COVID Ordinal Outcomes Scale on Study Day 3 Time: assessed on study day 3Description: We will determine the COVID Ordinal Scale on study day 8
Measure: COVID Ordinal Outcomes Scale on Study Day 8 Time: assessed on study day 8Description: We will determine the COVID Ordinal Scale on study day 29
Measure: COVID Ordinal Outcomes Scale on Study Day 29 Time: assessed on study day 29Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28 Time: Enrollment to Day 28Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Measure: Oxygen-free days through Day 28 Time: 28 days after randomizationDescription: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Measure: Ventilator-free days through Day 28 Time: 28 days after randomizationDescription: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Measure: Vasopressor-free days through Day 28 Time: 28 days after randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measure: Hospital-free days to Day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience seizure between randomization and day 28
Measure: Number of patients with seizures to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Measure: Number of patients with atrial or ventricular arrhythmia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience cardiac arrest between randomization and day 28
Measure: Number of patients with cardiac arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Measure: Number of patients with acute pancreatitis arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute kidney injury between randomization and day 28
Measure: Number of patients with acute kidney injury to day28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Measure: Number of patients with receipt of renal replacement therapy to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Measure: Number of patients with symptomatic hypoglycemia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28
Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Measure: Number of patients with severe dermatologic reaction to day 28 Time: 28 days after randomizationDescription: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge
Measure: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge Time: 28 days after randomizationThe 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 10 daysDescription: The number of days a patient is hospitalized
Measure: Duration of hospitalization Time: up to 10 daysDescription: 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: an average of 10 daysIn 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 7Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System
Description: To assess the improvement in oxygenation as determined by the PaO2/FiO2 ratio after treatment with study treatment
Measure: Oxygenation Improvement Time: 3 monthsDescription: To assess the improvement in pulmonary ventilation as determined by the Ventilation Index (VI), where VI = [RR x (PIP − PEEP) × PaCO2]/1000 after study treatment.
Measure: Pulmonary ventilation Improvement Time: 3 monthsDescription: To assess safety as judged by the frequency and severity of adverse events and severe adverse events (SAEs).
Measure: Safety Assessment of Frequency and Severity of Adverse Events Time: 3 monthsThis study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in hospitalized patients with moderate COVID-19 disease.
Description: Number and severity of adverse events
Measure: Phase 1: Frequency and Severity of Adverse Events (AE) Time: Up to 12 monthsDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Phase 1: Rate of clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.
Measure: Phase 1: Rate of clinical improvement Time: Up to 12 monthsDescription: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR in nasal and/or lower respiratory tract samples. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.
Measure: Phase 2: Time to Clearance of SARS-CoV-2 Time: Up to 28 daysDescription: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.
Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score Time: Up to 28 daysDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of Clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Number and severity of adverse events
Measure: Phase 2: Frequency and Severity of Adverse Events (AE) Time: up to 12 monthsDescription: Time to medical discharge as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by time to medical discharge Time: up to 12 monthsDescription: Hospital utilization will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by hospital utilization Time: up to 12 monthsDescription: Mortality rate will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by measuring mortality rate Time: up to 12 monthsDescription: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score Time: Up to 28 daysDescription: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).
Measure: Time to Pulmonary Clearance Time: Up to 28 daysDescription: For ventilatory support subjects, the days with supplemental oxygen-free.
Measure: Supplemental oxygen-free days Time: Up to 28 daysDescription: Proportion of subjects who need invasive or non-invasive ventilation
Measure: Proportion of subjects requiring ventilation Time: Up to 28 daysThe SARS-CoV2 virus causes severe or even fatal disease in a fraction of infected people. The clinical severity is based on a complicated pneumopathy with acute respiratory distress syndrome that can lead to multi-visceral failure. The underlying mechanism is a cytokinergic storm, an emerging facet of immunological dysregulation. This clinical trial is aimed to understand the mechanisms of this immunological dysregulation in order to identify therapeutic levers. The main objective is to understand the relationships between clinical severity, death or morbidity of resuscitation management, and immune status (i.e., immune pathways activated or not). Immune status will be investigated at many levels of organization (i.e., circulating leukocytes, cytokines and chemokines, transcripts). The secondary objectives are : - to understand what is responsible for clinical severity, viral load, or immune activation; - to highlight the consequences of immunological dysregulation on associated risks (i.e., immunosuppression leading to the emergence of infectious comorbidities) as well as the functioning of neurotransmission through metabolic pathway diversions. The impact of dysimmunity on these biological pathways will be assessed with a metabolomic analysis; - to understand the mechanisms of vulnerability related to the field. Moreover, while co-morbidities are likely to be a risk factor for severe disease progression, there are many situations in which they do not occur. Stress, with its neurovegetative and endocrinological dimensions, modulates the immune response. It is essential to know whether the stress response plays a role in immunological dysregulation. This analysis is a prerequisite for understanding the conditions of treatment with glucocorticoids. Angiotensin converting enzyme type 2 (ACE2) also plays a likely role in host viral infection. It is also thought to play an important role in the emergence of severe syndromes by affecting the quality of vascular response.
Description: Mortality
Measure: Mortality Time: 90 days following the enrollmentDescription: Th1/Th2/Th17/Treg balance, Type I Interferons and inflammation
Measure: Immune response - Plasma cytokine profile Time: Through study completion (90 days following the enrollment)Description: T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)
Measure: Immune response - Phenotype of circulating cells Time: Through study completion (90 days following the enrollment)Description: Number of days in intensive care unit
Measure: Severity criteria - Duration of stay in intensive care unit Time: 90 days following the enrollmentDescription: Number of days of hospitalization
Measure: Severity criteria - Duration of hospitalization stay Time: 90 days following the enrollmentDescription: Number of days out of hospital
Measure: Severity criteria - Duration of period out of hospital Time: 90 days following the enrollmentDescription: Number of days without mechanical ventilation (invasive/non-invasive)
Measure: Severity criteria - Duration without mechanical ventilation Time: 90 days following the enrollmentDescription: Number of days not being ventilated
Measure: Severity criteria - Duration without ventilation Time: 90 days following the enrollmentDescription: Number of days not being intubated
Measure: Severity criteria - Duration without intubation Time: 90 days following the enrollmentDescription: Number of transfusions
Measure: Severity criteria - Number of transfusions Time: 90 days following the enrollmentDescription: Number of days without cathecholamines
Measure: Severity criteria - Duration of the period without cathecholamines Time: 90 days following the enrollmentDescription: Number of days without dialysis
Measure: Severity criteria - Duration of the period without dialysis Time: 90 days following the enrollmentDescription: Sepsis-related Organ Failure Assessment (SOFA) Score
Measure: Severity criteria - SOFA Time: Through study completion (90 days following the enrollment)Description: Lung Injury Score (LIS)
Measure: Severity criteria - LIS Time: Through study completion (90 days following the enrollment)Description: SARS-Cov2 viral load will be measured in blood and in broncho-tracheal secretions
Measure: SARS-Cov2 viral load Time: Through study completion (90 days following the enrollment)Description: Co-infections and acquired infections (bacterial or fungal) in intensive care unit, in particular based on an all-site positive PCR for EBV and/or CMV and/or HSV
Measure: Emergence of concomitant infections Time: 90 days following the enrollmentDescription: T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)
Measure: Emergence of concomitant infections - Phenotype of circulating cells Time: Through study completion (90 days following the enrollment)Description: Heart rate variability
Measure: Stress physiological profile - Sympathetic tone Time: Through study completion (90 days following the enrollment)Description: Core temperature
Measure: Stress physiological profile - Temperature Time: Through study completion (90 days following the enrollment)Description: Quantity of glucocorticoids in the urine during 24 hours and at night
Measure: Stress physiological profile - Glucocorticoids Time: Through study completion (90 days following the enrollment)Description: ACE Polymorphism
Measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE Time: At enrollmentDescription: Protein expression of ACE2 vs. ACE1 and angiotensin II chain proteins
Measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1 Time: At enrollmentDescription: Diabete diagnosis
Measure: Comorbidities - diabetes Time: At enrollmentDescription: Heart disease diagnosis
Measure: Comorbidities - Heart disease Time: At enrollmentDescription: Organ failure diagnosis
Measure: Comorbidities - organ failure Time: At enrollmentDescription: GABA level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - GABA Time: Through study completion (90 days following the enrollment)Description: Glucocorticoid level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Glucocorticoid Time: Through study completion (90 days following the enrollment)Description: Tryptophan in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Tryptophan Time: Through study completion (90 days following the enrollment)Description: Serotonin level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Serotonin Time: Through study completion (90 days following the enrollment)Description: Dopamin level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Dopamin Time: Through study completion (90 days following the enrollment)Description: Catecholamines level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Cathecholamines Time: Through study completion (90 days following the enrollment)Description: Arachidonic acid derivatives level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives Time: Through study completion (90 days following the enrollment)Description: Endocannabinoids level in blood and urine
Measure: Plasma concentrations of several metabolic pathways - Endocannabinoids Time: Through study completion (90 days following the enrollment)The trial has two parts: a dose-finding part (Part A) with four dose cohorts (treatment groups) for each vaccine and one pre-defined and one optional dose level for a de-escalation approach and, a second part (Part B) dedicated to recruit expansion cohorts with dose levels which are selected from data generated in Part A. The vaccines BNT162a1, BNT162b1, and BNT162b2 will be administered using a Prime/Boost (P/B) regimen. The vaccine BNT162c2 will be administered using a Single dose (SD) regimen.
Description: For BNT162a1, BNT162b1, BNT162b2 (P/B): occurring up to 21±2 days after the prime immunization.
Measure: The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE): Time: 21 days following dose administrationDescription: For BNT162a1, BNT162b1, BNT162b2 (P/B): occurring up to 28±4 days after the boost immunization. For BNT162c2 (SD): The proportion of subjects with at least 1 unsolicited TEAE occurring up to 28±4 days after the immunization.
Measure: The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE): Time: 28 days following dose administrationDescription: Functional antibody responses at 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Fold increase in functional antibody titers 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Functional antibody responses at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationDescription: Fold increase in functional antibody titers at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationDescription: Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationELVIS COVID-19 is a pragmatic web-based Bayesian adaptive randomised controlled, parallel group trial of hypertonic saline nasal irrigation and gargling (HSNIG) compared to standard care in participants with clinically suspected or confirmed COVID-19 being managed at home.
Description: Time until participant reports well
Measure: Time to resolution of symptoms as defined by the single question 'how unwell do you feel today'. Time: Maximum of 14 daysDescription: Recorded using validated Wisconsin Upper Respiratory Symptom Survey-24 (WURSS-24) questionnaire and daily diaries. The WURSS-24 questionnaire assesses the interference on daily life and severity of symptoms on a scale of 1 (not at all) to 7 (severe)
Measure: Severity of all symptoms Time: 1-14 days or until the participant reports that they are wellDescription: Recorded using validated Wisconsin Upper Respiratory Symptom Survey-24 (WURSS-24) questionnaire and daily diaries. The WURSS-24 questionnaire assesses the interference on daily life and severity of symptoms on a scale of 1 (not at all) to 7 (severe)
Measure: The length of time for individual symptoms to resolve Time: 1-14 days or until the participant reports that they are wellDescription: Recorded using validated Wisconsin Upper Respiratory Symptom Survey-24 (WURSS-24) questionnaire and daily diaries. The WURSS-24 questionnaire assesses the interference on daily life and severity of symptoms on a scale of 1 (not at all) to 7 (severe)
Measure: Severity of individual symptoms Time: 1-14 days or until the participant reports that they are wellDescription: Number of participants and frequency of contacts
Measure: Contacting healthcare (NHS 24, OOH, GP) Time: 1-14 days or until the participant reports that they are wellDescription: Number of participants and frequency of contacts
Measure: Participants needing GP appointments Time: 1-14 days or until the participant reports that they are wellDescription: Number of participants
Measure: Participants attending hospital Time: 1-14 days or until the participant reports that they are wellDescription: Number of days
Measure: Length of stay in hospital if admitted Time: 1-14 days or until the participant reports that they are wellDescription: Number of participants
Measure: Number of participants reporting over the counter medication use Time: 1-14 days or until the participant reports that they are wellDescription: Number of people within participant's household who develop symptoms
Measure: Reduction in transmission to household contacts Time: 1-14 days or until the participant reports that they are wellDescription: Number of participants in intervention arm reporting side effects
Measure: Number of participants reporting side effects of nasal irrigation Time: 1-14 days or until the participant reports that they are wellDescription: Participants asked if they have experienced common side effects or other and to rate the severity on a 7 point scale of 'Did not have this side effect' to 'severe'
Measure: Types and severity of side effects reported Time: 1-14 days or until the participant reports that they are wellDescription: Estimated cost requested when participant states over the counter medication used
Measure: Cost of over the counter medication used Time: 1-14 days or until the participant reports that they are wellThe use of both levamisole & Isoprinosine has both synergistic and complementary effect in the treatment of COVID 19 infection
Description: Improvement of fever in degrees celsius
Measure: COVID 19 induced fever in both groups Time: 4 weeksDescription: improvement of dyspnea by normalization of respiratory rate
Measure: COVID 19 induced dyspnea in both groups Time: 4 weeksDescription: PCR of COVID 19 changes from positive to negative
Measure: COVID 19 viral load in both groups Time: 4 weeksDescription: CRP in mg/dL
Measure: laboratory clearance in both groups: CRP in mg/dL Time: 4 weeksThe aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.
The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.
Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)
Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease Time: Measuring during 28-day period since randomization (Intention to treat analysis)Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)
Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization Time: Measuring during 14-day period since randomizationDescription: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.
Measure: Time to clinical improvement Time: Measuring during 28-day period since randomizationDescription: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;
Measure: Time to clinical failure Time: Measuring during 28-day period since randomizationDescription: Proportion of participants with hospitalization for any cause
Measure: Hospitalization for any cause Time: Measuring during 28-day period since randomizationDescription: Evaluation of adverse events evaluated as associated to any of study arms
Measure: Proportion of participants who presented with adverse events Time: Measuring during 28-day period since randomizationDescription: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.
Measure: Time to improvement on respiratory scale symptoms Time: Measuring during 28-day period since randomizationThe aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic . VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2.
This Phase 2/3 trial evaluates four treatment strategies for non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, in which participants will receive NA-831 or Atazanavir with or without Dexamethasone.
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: 1. Time (Hours) to recovery Time: [ Time Frame: 36 days ]Description: 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: [ Time Frame: 36 days ]