Covid 19 Research using Clinical Trials (Home Page)
SarilumabWiki
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Correlated Drug Terms (30)
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1425 | Macrolide administered for up to 14 days Wiki | 0.45 |
| drug1227 | Interferon-β1a Wiki | 0.45 |
| drug1424 | Macrolide administered for 3-5 days Wiki | 0.45 |
| drug949 | Fixed-duration Hydrocortisone Wiki | 0.45 |
| drug1932 | Protocolised mechanical ventilation strategy Wiki | 0.45 |
| drug749 | Dexamethasone (high dose) Wiki | 0.45 |
| drug2254 | Shock-dependent hydrocortisone Wiki | 0.45 |
| drug1092 | Hydroxychloroquine + lopinavir/ritonavir Wiki | 0.45 |
| drug1820 | Piperacillin-tazobactam Wiki | 0.45 |
| drug156 | Amoxicillin-clavulanate Wiki | 0.45 |
| drug950 | Fixed-duration higher dose Hydrocortisone Wiki | 0.45 |
| drug532 | Ceftriaxone Wiki | 0.45 |
| drug2296 | Standar of care Wiki | 0.45 |
| drug946 | Five-days oseltamivir Wiki | 0.45 |
| drug1523 | Moxifloxacin or Levofloxacin Wiki | 0.45 |
| drug531 | Ceftaroline Wiki | 0.45 |
| drug2472 | Ten-days oseltamivir Wiki | 0.45 |
| drug2499 | Therapeutic anticoagulation Wiki | 0.32 |
| drug2263 | Simvastatin Wiki | 0.32 |
| drug2062 | Relatlimab Wiki | 0.32 |
| drug1610 | Nivolumab Wiki | 0.26 |
| drug159 | Anakinra Wiki | 0.17 |
| drug1372 | Lopinavir/ritonavir Wiki | 0.14 |
| drug2662 | Vitamin C Wiki | 0.13 |
| drug658 | Convalescent plasma Wiki | 0.11 |
| drug1613 | No intervention Wiki | 0.11 |
| drug1086 | Hydroxychloroquine Wiki | 0.09 |
| drug2527 | Tocilizumab Wiki | 0.08 |
| drug262 | Azithromycin Wiki | 0.08 |
| drug1822 | Placebo Wiki | 0.03 |
Correlated MeSH Terms (7)
| Name (Synonyms) | Correlation | |
|---|---|---|
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.04 |
| D055371 | Acute Lung Injury NIH | 0.04 |
| D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.04 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.04 |
| D018352 | Coronavirus Infections NIH | 0.04 |
| D011014 | Pneumonia NIH | 0.03 |
| D007239 | Infection NIH | 0.03 |
There are 5 clinical trials
Clinical Trials
1 Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.
NCT02735707 Community-acquired Pneumonia, Influenza, COVID-19 Drug: Fixed-duration Hydrocortisone Drug: Shock-dependent hydrocortisone Drug: Ceftriaxone Drug: Moxifloxacin or Levofloxacin Drug: Piperacillin-tazobactam Drug: Ceftaroline Drug: Amoxicillin-clavulanate Drug: Macrolide administered for 3-5 days Drug: Macrolide administered for up to 14 days Drug: Five-days oseltamivir Drug: Ten-days oseltamivir Drug: Lopinavir/ritonavir Drug: Hydroxychloroquine Drug: Hydroxychloroquine + lopinavir/ritonavir Drug: Interferon-β1a Drug: Anakinra Drug: Fixed-duration higher dose Hydrocortisone Drug: Tocilizumab Drug: Sarilumab Drug: Vitamin C Drug: Therapeutic anticoagulation Drug: Simvastatin Drug: Convalescent plasma Other: Protocolised mechanical ventilation strategy MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: All-cause mortality Time: Day 90
Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and not receiving organ support in ICU Time: Day 21
Secondary Outcomes
Measure: ICU Mortality Time: Day 90
Measure: ICU length of stay Time: Day 90
Measure: Hospital length of stay Time: Day 90
Measure: Ventilator free days Time: Day 28
Measure: Organ failure free days Time: Day 28
Measure: All-cause mortality Time: 6 months
Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 months
Measure: Proportion of intubated patients who receive a tracheostomy Time: Day 28
Description: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Measure: Destination at time of hospital discharge Time: Free text Day 90
Measure: Readmission to the index ICU during the index hospitalization Time: Day 90
Measure: World Health Organisation 8-point ordinal scale outcome Time: Hospital discharge
Other Outcomes
Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital discharge
Description: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital discharge
Description: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.
Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death Time: Day 90, censored at hospital discharge
Description: Antiviral Domain specific outcome. Only required at selected sites.
Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens Time: Day 3, up to Day 7
Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint
Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing) Time: Day 90, censored at hospital discharge
2 An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19
Primary Outcomes
Measure: All-cause mortality Time: Day 90Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and not receiving organ support in ICU Time: Day 21Secondary Outcomes
Measure: ICU Mortality Time: Day 90Measure: ICU length of stay Time: Day 90
Measure: Hospital length of stay Time: Day 90
Measure: Ventilator free days Time: Day 28
Measure: Organ failure free days Time: Day 28
Measure: All-cause mortality Time: 6 months
Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 monthsMeasure: Proportion of intubated patients who receive a tracheostomy Time: Day 28
Description: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Measure: Destination at time of hospital discharge Time: Free text Day 90Measure: Readmission to the index ICU during the index hospitalization Time: Day 90
Measure: World Health Organisation 8-point ordinal scale outcome Time: Hospital discharge
Other Outcomes
Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital dischargeDescription: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital dischargeDescription: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.
Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death Time: Day 90, censored at hospital dischargeDescription: Antiviral Domain specific outcome. Only required at selected sites.
Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens Time: Day 3, up to Day 7Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint
Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing) Time: Day 90, censored at hospital dischargePhase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata. Phase 3 Cohort 1: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline. Phase 3 Cohort 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.
NCT04315298 COVID-19 Drug: Sarilumab Drug: Placebo
Primary Outcomes
Description: Phase 2
Measure: Percent change in C-reactive protein (CRP) levels in patients with serum IL-6 level greater than the upper limit of normal Time: Day 4Description: Phase 3 Cohort 1 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with critical COVID-19 receiving mechanical ventilation at baseline Time: Up to day 22Description: Phase 3 Cohort 2
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with COVID-19 receiving mechanical ventilation at baseline Time: Up to day 22Secondary Outcomes
Description: Phase 2
Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal Time: Up to day 29Description: Phase 2
Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale reporting in severe or critical patients with all IL-6 levels Time: Up to day 29Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever Time: Up to day 29Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by clinical severity Time: Up to day 29Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels Time: Up to day 29Description: Phase 2 Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours Time: Up to day 29Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by clinical severity Time: Up to day 29Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels Time: Up to day 29Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to resolution of fever and improvement in oxygenation for at least 48 hours Time: Up to day 29Description: Phase 2
Measure: Mean change in the 7-point ordinal scale Time: Up to day 29Description: Phase 2
Measure: Percentage of patients in each clinical status category using the 7-point ordinal scale Time: Up to day 29Description: Phase 2 NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
Measure: Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours Time: Up to day 29Description: Phase 2
Measure: Change from baseline in NEWS2 scoring system Time: Up to day 29Description: Phase 2 Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)
Measure: Number of days with fever Time: Up to day 29Description: Phase 2
Measure: Proportion of patients alive, off oxygen Time: At day 29Description: Phase 2
Measure: Number of days of resting respiratory rate >24 breaths/min Time: Up to day 29Description: Phase 2
Measure: Number of days with hypoxemia Time: Up to day 29Description: Phase 2
Measure: Number of days of supplemental oxygen use Time: Up to day 29Description: Phase 2
Measure: Time to saturation ≥94% on room air Time: Up to day 29Description: Phase 2
Measure: Number of ventilator free days in the first 28 days Time: Baseline to day 29Description: Phase 2
Measure: Number of patients requiring initiation of mechanical ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring non-invasive ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring the use of high flow nasal cannula Time: Up to day 29Description: Phase 2
Measure: Number of patients admitted into an intensive care unit (ICU) Time: Up to day 29Description: Phase 2
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2
Measure: Number of deaths due to any cause Time: Up to day 60Description: Phase 3
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale Time: Up to day 22Description: Phase 3 Defined as discharged, or alive without supplemental oxygen use or at pre-COVID oxygen use
Measure: Proportion of patients who recover Time: Up to day 22Description: Phase 3
Measure: Proportion of deaths Time: Through day 29Description: Phase 3
Measure: Proportion of patients alive not receiving mechanical ventilation Time: At day 22Description: Phase 3
Measure: Proportion of patients alive not requiring extracorporeal membrane oxygenation (ECMO) Time: At day 22Description: Phase 3
Measure: Proportion of patients with a 2-point improvement in clinical status on the 7-point ordinal scale Time: Up to day 22Description: Phase 3
Measure: Time to at least 1-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Time to at least 2-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Proportion of patients receiving mechanical ventilation Time: Up to day 22Description: Phase 3
Measure: Proportion of patients receiving ECMO Time: Up to day 22Description: Phase 3
Measure: Proportion of patients discharged and alive Time: At day 22Description: Phase 3 Defined as discharged or alive without supplemental oxygen use or at pre-COVID oxygen use
Measure: Time to recovery Time: Up to day 29Description: Phase 3
Measure: Proportion of deaths Time: Through day 60Description: Phase 3
Measure: Time to death due to any cause Time: Through day 60Description: Phase 3
Measure: Number of ventilator free days Time: Up to day 29Description: Phase 3
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with serious adverse events Time: Up to Day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with Grade 4 neutropenia (ANC <500/mm3) Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia (ANC <500/mm3) Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with hypersensitivity reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with infusion reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with gastrointestinal perforation Time: Up to day 29Description: Phase 2 and Phase 3
Measure: White blood cell count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Hemoglobin levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Platelet count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Creatinine levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Total bilirubin level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Alanine aminotransferase (ALT) level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Aspartate aminotransferase (AST) level Time: Up to day 29 if still hospitalized3 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Sarilumab administration to patients enrolled in the CORIMUNO-19 cohort. Sarilumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Sarilumab will receive standard of care. Outcomes of Sarilumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.
NCT04324073 Corona Virus Infection Drug: Sarilumab MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Time: 14 daysDescription: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4 Time: 4 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 Time: 14 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event. Scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9
Measure: WHO progression scale at day 4 Time: 4 daysSecondary Outcomes
Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysMeasure: 28-day ventilator free-days Time: 28 days
Description: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 days4 Efficacy of Sarilumab + Azithromycin + Hydroxychloroquine, and Sarilumab Alone, for Adult Patients Hospitalized With Moderate to Severe COVID-19: a Multicenter Open-label 1:1 Randomized Controlled Trial
The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering investigational treatments administration to patients enrolled in the CORIMUNO-19 cohort (NCT04324047). Sarilumab+Azithromycin+Hydroxychloroquine, or Sarilumab only will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation. All patients will receive standard of care along with randomized investigational treatments. Outcomes of included patients will be compared between groups as well as with outcomes of patients in the CORIMUNO-19 cohort treated with other immune modulators or standard of care.
NCT04341870 COVID19 SARS-CoV-2 Infection Drug: Sarilumab Drug: Azithromycin Drug: Hydroxychloroquine
Primary Outcomes
Description: Events considered are: need for ventilation (including invasive and non invasive ventilation), transfer to the Intensive Care Unit, death or new do-not-resuscitate (DNR) decision in the absence ventilation and outside ICU.
Measure: Need for ventilation (including invasive and non invasive ventilation), intensive care or death Time: 14 daysSecondary Outcomes
Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: Early improvement: OMS progression scale <= 5 Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: OMS progression scale Time: 4, 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: Number of ICU-free days alive
Measure: ICU-free days alive Time: 14, 28 and 90 daysDescription: Number of ventilation(invasive or non invasive)-free days alive
Measure: Ventilation-free days alive Time: 14 and 28 daysDescription: Number of hospital-free days alive
Measure: Hospital-free days alive Time: 14, 28 and 90 daysDescription: Number of oxygen therapy-free days alive
Measure: Oxygen therapy-free days alive Time: 14 and 28 daysDescription: SARS-CoV-2 viral load measurement by rtPCR
Measure: Time to negative viral excretion Time: 90 daysDescription: Immunophenotyping and multiplex cytokines (blood sample)
Measure: Immunophenotyping and multiplex cytokines Time: 8 days5 Randomized Open Pilot Study to Evaluate the Efficacy of Subcutaneous Sarilumab in Patients With Moderate-severe COVID-19 Infection
The global health emergency created by the rapid spread of the SARS-CoV-2 coronavirus has pushed healthcare services to face unprecedent challenges to properly manage COVID-19 severe and critical manifestations affecting a wide population in a short period of time. Clinicians are committed to do their best with a great uncertainty in this evolving crisis. Off label use of plenty of drugs has arisen the need for clinical trials to demonstrate their true role in the therapy. Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are available yet. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptors to inhibit IL-6 signalling, licensed in a subcutaneous route administration.
NCT04357808 Covid-19 Drug: Sarilumab Other: Standar of care MeSH:Infection
Primary Outcomes
Description: Score ranges 1-7 Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized
Measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation Time: 7 days from enrolmentDescription: Days from the date of enrolment to the date of discharge
Measure: Duration of hospitalisation (days) Time: 30 days from enrolmentDescription: Number of deaths
Measure: Death Time: 30 days from enrolmentSecondary Outcomes
Description: Time to become afebrile for a minimum period of 48 hours, without antipyretics
Measure: Time to become afebrile (days) Time: 30 days from enrolmentDescription: Days from enrolment to non-invasive mechanical ventilation
Measure: Time to non-invasive mechanical ventilation (days) Time: 30 days from enrolmentDescription: Days from enrolment to invasive mechanical ventilation
Measure: Time to invasive mechanical ventilation (days) Time: 30 days from enrolmentDescription: Days from enrolment to supplementary oxygen therapy withdrawal
Measure: Time to independence from supplementary oxygen therapy (days) Time: 30 days from enrolmentDescription: Scale ranges 1-7: Death Hospitalized, with mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Hospitalized, with non-invasive mechanical ventilation, a mask with a reservoir or oxygen with high flow nasal goggles. Hospitalized with oxygen supplement Hospitalized, without oxygen supplement, but in need of continued medical care (related or not with COVID) Hospitalized, without oxygen supplement and without the need for continued medical care Not hospitalized
Measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation Time: 14 days from enrolmentOther Outcomes
Description: Number of adverse events and number of patients with adverse events
Measure: Incidence of serious and non-serious adverse events. Time: 30 days after enrolmentDescription: Number of adverse reactions that requires discontinuation of any drug in the study
Measure: Discontinuation due to adverse reactions Time: 30 days after enrolment