Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI

Corona Virus Infection Clinical Trial

— CORIMUNO-SARI  

Official title:

Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04324073
• Other study ID #: APHP200375-2
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: March 27, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 239
• Est. completion date: December 31, 2021
• Est. primary completion date: March 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort

2. Patients belonging to one of the 2 following groups:

• Group 1: patients not requiring ICU at admission with moderate and severe pneumopathy according to the OMS Criteria of severity of COVID pneumopathy.

Moderate cases :

Cases meeting all of the following criteria:

• Showing fever and respiratory symptoms with radiological findings of pneumonia.

• Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 >97% Severe cases

Cases meeting any of the following criteria:

• Respiratory distress (?30 breaths/ min);

• Oxygen saturation=93% at rest in ambient air; or Oxygen saturation =97 % with O2 > 5L/min.

• PaO2/FiO2?300mmHg

• Group 2: patients requiring ICU based on Criteria of severity of COVID pneumopathy.

• Respiratory failure and requiring mechanical ventilation

• No do-not-resuscitate order (DNR order)

Exclusion Criteria:

• Patients with exclusion criteria to the CORIMUNO-19 cohort.

• Known hypersensitivity to Sarilumab or to any of their excipients.

• Pregnancy

• Current documented bacterial infection

• Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:

• Absolute neutrophil count (ANC) = 1.0 x 109/L

• Haemoglobin level: no limitation

• Platelets (PLT) < 50 G /L

• SGOT or SGPT > 5N

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections
• Severe Acute Respiratory Syndrome
• Virus Diseases

Intervention

Drug:
• Sarilumab
(an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1

Locations

Country	Name	City	State
France	Kremlin Bicetre hospital APHP	Le Kremlin-Bicêtre	Ile De France
France	Cochin Aphp	Paris	Ile De France
France	HEGP	Paris	Ile De France
France	NECKER Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without needs of ventilator utilization at day 14.	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.	14 days
Primary	WHO progression scale <=5 at day 4	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	4 days
Primary	Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14	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.	14 days
Primary	WHO progression scale at day 4	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	4 days
Secondary	WHO progression scale	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	7 and 14 days
Secondary	Survival	Overall survival	14, 28 and 90 days
Secondary	28-day ventilator free-days		28 days
Secondary	respiratory acidosis at day 4	arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of =60 mm Hg for >6 hours	4 days
Secondary	PaO2/FiO2 ratio	evolution of PaO2/FiO2 ratio	day 1 to day 14
Secondary	time to oxygen supply independency	time to oxygen supply independency	14 days
Secondary	duration of hospitalization	duration of hospitalization	90 days
Secondary	time to negative viral excretion	time to negative viral excretion	90 days
Secondary	time to ICU discharge	time to ICU discharge	90 days
Secondary	time to hospital discharge	time to hospital discharge	90 days