Name (Synonyms) | Correlation | |
---|---|---|
drug2068 | Remdesivir placebo Wiki | 0.37 |
drug266 | Azithromycin 500 milligram (mg) oral Tablet Wiki | 0.26 |
drug1471 | Merimepodib Wiki | 0.26 |
drug1477 | Mesenchymal stem cells Wiki | 0.26 |
drug118 | Active COVID-19 disease Wiki | 0.26 |
drug1131 | Hydroxychloroquine, Doxycycline Wiki | 0.26 |
drug1528 | Multifrequency Bioimpedance Spectroscopy Wiki | 0.26 |
drug1855 | Placebo solution Wiki | 0.26 |
drug1479 | Messaging Wiki | 0.26 |
drug782 | Docetaxel Wiki | 0.26 |
drug1223 | Interferon-Alpha2B Wiki | 0.26 |
drug1533 | MuscleSound Ultrasound Wiki | 0.26 |
drug1130 | Hydroxychloroquine, Clindamycin, Primaquine - low dose. Wiki | 0.26 |
drug1958 | Q-NRG Metobolic Cart Device Wiki | 0.26 |
drug1127 | Hydroxychloroquine, Azithromycin Wiki | 0.26 |
drug330 | Berzosertib Wiki | 0.26 |
drug656 | Convalescent Serum Wiki | 0.26 |
drug2065 | Relaxation Therapy Wiki | 0.26 |
drug2 | (Standard of Care) SoC Wiki | 0.26 |
drug1129 | Hydroxychloroquine, Clindamycin, Primaquine - high dose. Wiki | 0.26 |
drug1319 | Laboratory Biomarker Analysis Wiki | 0.26 |
drug1128 | Hydroxychloroquine, Clindamycin Wiki | 0.26 |
drug522 | Carboplatin Wiki | 0.18 |
drug595 | Cognitive Behavioral Therapy Wiki | 0.18 |
drug960 | Follow up Wiki | 0.18 |
drug824 | Eculizumab Wiki | 0.18 |
drug1485 | Methylprednisolone Sodium Succinate Wiki | 0.18 |
drug1441 | Matching Placebo Wiki | 0.18 |
drug1219 | Interferon Beta-1A Wiki | 0.13 |
drug2765 | blood sample Wiki | 0.11 |
drug2319 | Standard of Care Wiki | 0.10 |
drug315 | Baricitinib Wiki | 0.10 |
drug2527 | Tocilizumab Wiki | 0.10 |
drug1374 | Losartan Wiki | 0.09 |
drug1372 | Lopinavir/ritonavir Wiki | 0.08 |
drug1484 | Methylprednisolone Wiki | 0.08 |
drug1822 | Placebo Wiki | 0.07 |
drug2326 | Standard of care Wiki | 0.06 |
drug1086 | Hydroxychloroquine Wiki | 0.05 |
Name (Synonyms) | Correlation | |
---|---|---|
D001010 | Anxiety, Separation NIH | 0.26 |
D000072861 | Phobia, Social NIH | 0.26 |
D016584 | Panic Disorder NIH | 0.26 |
D000379 | Agoraphobia NIH | 0.26 |
D010698 | Phobic Disorders NIH | 0.18 |
D011471 | Prostatic Neoplasms NIH | 0.15 |
D002277 | Carcinoma NIH | 0.12 |
D018352 | Coronavirus Infections NIH | 0.11 |
D018450 | Disease Progression NIH | 0.07 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.06 |
D004194 | Disease NIH | 0.05 |
D001008 | Anxiety Disorders NIH | 0.04 |
D014777 | Virus Diseases NIH | 0.03 |
D011014 | Pneumonia NIH | 0.03 |
D007239 | Infection NIH | 0.03 |
D013577 | Syndrome NIH | 0.03 |
D055371 | Acute Lung Injury NIH | 0.03 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.03 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.02 |
D003141 | Communicable Diseases NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0000756 | Agoraphobia HPO | 0.26 |
HP:0012125 | Prostate cancer HPO | 0.15 |
HP:0030731 | Carcinoma HPO | 0.12 |
HP:0002090 | Pneumonia HPO | 0.03 |
There are 15 clinical trials
In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the availability of remdesvir as a potential antiviral agent based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with mild or moderate COVID-19.
Description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalisation and alleviation criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
Measure: Time to Clinical recoveryTime to Clinical Recovery (TTCR) Time: up to 28 daysDescription: baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
Measure: All cause mortality Time: up to 28 daysDescription: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
Measure: Frequency of respiratory progression Time: up to 28 daysIn December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of remdesvir as a potential antiviral agent, based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with severe COVID-19.
Description: The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
Measure: Time to Clinical Improvement (TTCI) [Censored at Day 28] Time: up to 28 daysDescription: Clinical status, assessed by the ordinal scale at fixed time points (days 7, 14, 21, and 28).
Measure: Clinical status Time: days 7, 14, 21, and 28Description: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
Measure: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours. Time: up to 28 daysThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 3 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8-point ordinal scale Time: Day 15Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 29-day mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of = 2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale on Day 11.
Description: The odds ratio represents the odds of improvement in the ordinal scale between the treatment groups. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration 7. Not hospitalized.
Measure: The Odds of Ratio for Improvement on a 7-point Ordinal Scale on Day 11 Time: Day 11The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.
Description: The odds ratio represents the odds of improvement in the ordinal scale between the treatment groups. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration 7. Not hospitalized.
Measure: The Odds of Ratio for Improvement on a 7-point Ordinal Scale on Day 14 Time: Day 14Disease caused by 2019 Novel Coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC (this treatment arm has been ceased since June 29, 2020) + Lopinavir/Ritonavir plus interferon ß-1a versus SoC (this treatment arm has been ceased since June 29, 2020) + Hydroxychloroquine (this treatment arm has been ceased since May 24, 2020). Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.
Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale Time: Day 15Description: Time to an improvement of one category from admission on an ordinal scale. Time to an improvement of two categories from admission on an ordinal scale. Time to discharge (categories 1 or 2 of ordinal scale) from admission. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.
Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale Time: Days 3, 5, 8, 11, 15 and 29Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.
Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Time: Days 3, 5, 8, 11, 15 and 29Description: • Duration of hospitalization (days).
Measure: Hospitalization Time: 29 daysDescription: Rate of mortality
Measure: Mortality Time: In hospital, Day 28, Day 90Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of lopinavir Time: Days 1, 3, 5, 8 and 11Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of hydroxychloroquine Time: Days 1, 3, 5, 8 and 11The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.
Description: All cause in-hospital mortality
Measure: In-hospital mortality Time: 3 weeksThe primary objective of this study is to provide expanded access of remdesivir (RDV) for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
Diagnostic determination of disease and treatment responses has been limited to qualitative imaging, measurement of serum markers of disease, and sampling of tissue. In each of these instances, there is a built in error either due to sensitivity and specificity issues, clinician interpretation of results, or acceptance of the use of an indirect marker (blood test) of what is happening elsewhere in the body - at the tissue level. The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons [1] provides the first and only patented test (#9566037) - along with the associated submitted patent applications ruled to be covered under #9566037 - that quantitatively measures changes in tissue resulting from inter alia a disease process. This includes inter alia coronary artery disease (CAD), cancer and infectious/inflammatory processes including CoVid-19 pneumonia (CVP) resulting from the metabolic and regional blood flow differences (RBFDs) caused by these diseases. The purpose of this paper is to make clinicians and researchers aware of this proposed method for investigating the prevalence and severity of CVP - in addition to providing rapid determination of treatment response in each patient, directing treatment decisions; thereby reducing the loss of time, money, resources and patient lives.
Description: Measured improvement in tissue as measured using FMTVDM
Measure: Improvement in FMTVDM Measurement with nuclear imaging. Time: 72 hoursDescription: Extubation
Measure: Ventilator status Time: 7 daysDescription: Self explanatory
Measure: Survival status Time: 30 daysThis study is a retrospective cohort trial to assess the efficacy of remdesivir in hospitalized adult patients diagnosed with COVID-19. The study is a multicenter trial which will be carried out on different sites in France. This trial is retrospective and will analyze the data collected during treatment.
Description: Study the prognostic factors of the clinical course of patients on Day 15 under treatment with remdesivir. Clinical progress will be categorized using a 7-point ordinal scale.
Measure: Clinical course on Day 15. Time: 15 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 3
Measure: Clinical course on Day 3. Time: 3 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 8
Measure: Clinical course on Day 8 Time: 8 daysDescription: Explore the prognostic factors of the clinical course of patients on Day11
Measure: Clinical course on Day 11. Time: 11 daysDescription: Explore the prognostic factors of the clinical course of patients on D29.
Measure: Clinical course on Day 29. Time: 29 daysDescription: Duration of treatment with remdesivir
Measure: Duration of treatment Time: 29 daysDescription: PaO2 / FiO2 and artificial ventilation; platelets; bilirubin; average blood pressure and use of vasoactive drugs; Glasgow score; creatinine.
Measure: Sepsis-related Organ Failure Assessment score Time: Day 3, 8, 11, 15 and 29Description: Duration without mechanical ventilation within 29 days of initiation of treatment with remdesivir
Measure: Duration without mechanical ventilation Time: 29 daysDescription: Mortality at 29 days after initiation of treatment with remdesivir.
Measure: Mortality Time: 29 daysDescription: Evaluate the safety of the treatment with cumulative incidence of grade 3 and 4 adverse events (AEs).
Measure: cumulative incidence of grade 3 and 4 adverse events (AEs). Time: 29 daysACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.
Measure: Time to recovery Time: Day 1 through Day 29Description: PT reported as international normalized ratio (INR).
Measure: Change from baseline in prothrombin time (PT) Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 28-day mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of = 2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.
Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 28The purpose of this study is to assess the safety and efficacy of merimepodib (MMPD) oral solution when administered in combination with remdesivir in adult patients with advanced COVID-19.
Description: Proportion of subjects alive at Day 28 who are not hospitalized or if hospitalized are free of respiratory failure
Measure: Number of subjects not hospitalized or, if hospitalized, free of respiratory failure Time: Day 0 to Day 28Description: Number of Adverse Events (AEs) and number & percentage of subjects experiencing AEs after administration of the first dose of study drug
Measure: Adverse Events Time: Day 0 to Day 56Description: Change in NIAID 8-point ordinal scale, where 1=Death and 8=Not hospitalized, no limitations on activities
Measure: National Institute of Allergy and Infectious Disease (NIAID) 8-Point Ordinal Scale Time: Day 0 to Day 28Description: Duration of fever
Measure: Temperature Time: Day 0 to Day 37Description: Number of deaths
Measure: Death Time: Day 0 to Day 56Description: Need and duration of mechanical ventilation
Measure: Mechanical ventilation Time: Day 0 to Day 56Description: Duration of vasopressor support
Measure: Vasopressor Support Time: Day 0 to Day 56Description: Duration of oxygen therapy via mechanical ventilation, face mask or nasal cannula
Measure: Oxygen Therapy Time: Day 0 to Day 37Description: Time to cessation of viral shedding based on absence of SARS-CoV-2 in a PCR based COVID-19 test
Measure: Cessation of Viral Shedding Time: Day 0 to Day 37Description: Change in SpO2/FiO2
Measure: Change in Oxygen Saturation/Fraction of Inspired Oxygen Time: Day 0 to Day 37The primary objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of remdesivir (RDV) in participants with laboratory-confirmed coronavirus disease 2019 (COVID-19) aged 0 days to < 18 years.
Description: Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Measure: Plasma Concentrations of Remdesivir (RDV) and Metabolites Time: Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hoursDescription: The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1.) Death 2.) Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) 3.) Hospitalized, on non-invasive ventilation or high flow oxygen devices 4.) Hospitalized, requiring low flow supplemental oxygen 5.) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6.) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration) 7.) Not hospitalized.
Measure: Clinical Improvement on a 7-point Ordinal Scale Time: First dose date up to 10 daysDescription: Confirmed negative PCR is defined by 2 consecutive negative PCR results.
Measure: Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result Time: First dose date up to 10 daysDescription: The PEWS is measured by 3 components, including 1.) behavior, 2.) perfusion assessed by capillary refill and heart rate, and 3.) respiratory status assessed by respiratory rate, effort, and oxygen requirement. The score ranges between zero to 9 point, with 9 point representing the highest severity level.
Measure: Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale Time: First dose date up to 10 daysDescription: Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Measure: Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD) Time: Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hours