CORIMUNO-19 - Tocilizumab Trial - TOCI (CORIMUNO-TOCI)

Phase 2

• Conditions: Corona Virus Infection
• Interventions: Drug: Tocilizumab

• Registration Number: NCT04331808
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The overall objective of the study is to determine the therapeutic effect and tolerance of Tocizilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the COVIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-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 Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-03
• Study Start: 2020-03-30
• Study First Submitted: 2020-03-31
• Study First Submitted QC: 2020-03-31
• Study First Posted: 2020-04-02
• Last Update Submitted: 2020-04-26
• Last Update Posted: 2020-04-28
• Primary Completion: 2021-03-31
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

1. Patients included in the CORIMUNO-19 cohort

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

   • Group 1: Cases meeting all of the following criteria

     • Requiring more than 3L/min of oxygen
     • OMS/WHO progression scale = 5
     • No NIV or High flow

   • Group 2: Cases meeting all of the following criteria

     • Respiratory failure AND (requiring mechanical ventilation OR NIV OR High flow)
     • WHO progression scale >=6
     • No do-not-resuscitate order (DNR order)

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TOCILIZUMAB	Tocilizumab	Tocilizumab 8mg/kg D1 and if no response (no decrease of oxygen requirement) a second injection at D3.

Primary Outcome Measures

Name	Time	Method
Survival without needs of ventilator utilization at day 14. Group 1	14 days	Group 1. 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.
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14. Group 2.	14 days	Group 2. 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.
WHO progression scale <=5 at day 4. Group 1.	4 days	Group 1. 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
WHO progression scale at day 4. Group 2.	4 days	Group 2 Early end point : proportion of patients with a decrease of WHO score of at least 1 point at day 4.; 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

Secondary Outcome Measures

Name	Time	Method
28-day ventilator free-days	28 days
PaO2/FiO2 ratio	day 1 to day 14	evolution of PaO2/FiO2 ratio
time to negative viral excretion	90 days	time to negative viral excretion
time to hospital discharge	90 days	time to hospital discharge
time to ICU discharge	90 days	time to ICU discharge
respiratory acidosis at day 4	4 days	arterial blood pH of \<7.25 with a partial pressure of arterial carbon dioxide \[Paco2\] of ≥60 mm Hg for \>6 hours
WHO progression scale	7 and 14 days	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
time to oxygen supply independency	14 days	time to oxygen supply independency
duration of hospitalization	90 days	duration of hospitalization
Survival	14, 28 and 90 days	Overall survival

Trial Locations

Locations (8)

APHP- Hopital Tenon; 🇫🇷 Paris, France

APHP - Beaujon; 🇫🇷 Paris, France

APHP - Hopital Necker; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

APHP - Pitié Salpêtrière; 🇫🇷 Paris, France

APHP - Bichat; 🇫🇷 Paris, France

APHP - Saint Louis; 🇫🇷 Paris, France