Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19

Phase 2

Completed

• Conditions: RNA Virus Infections; Coronavirus Infection; SARS (Severe Acute Respiratory Syndrome); Virus Diseases; Coronaviridae Infections; Respiratory Tract Disease; Respiratory Tract Infections; Nidovirales Infections
• Interventions: Drug: Dexamethasone; Drug: Tocilizumab

• Registration Number: NCT04476979
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone 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 Dexamethasone alone or Dexamethasone +Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort.

Tocilizumab 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 Tocilizumab will receive standard of cares.

Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care (including Dexamethasone) treated patients

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-16
• Study First Submitted: 2020-07-16
• Study First Submitted QC: 2020-07-16
• Study First Posted: 2020-07-20
• Primary Completion: 2021-06-01
• Study Completion: 2021-08-11
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-29
• Last Update Posted: 2024-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 453

Inclusion Criteria

1. Patients included in the CORIMUNO-19 cohort

2. Patients belonging to the following group:

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

Exclusion Criteria

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

• Known hypersensitivity to Tocilizumab or DXM or to any of their excipients.

• Pregnancy

• Current documented bacterial infection not controlled by antibiotics.

• certain evolving viral diseases (especially active herpes, chickenpox, shingles),

• psychotic states still not controlled by treatment,

• live vaccines in the previous 4 weeks,

• Active tuberculosis or disseminated strongyloidiasis

• 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
Dexamethasone	Dexamethasone	Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
Dexamethasone + Tocilizumab	Dexamethasone	Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) +Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
Dexamethasone + Tocilizumab	Tocilizumab	Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) +Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3

Primary Outcome Measures

Name	Time	Method
Survival without needs of invasive ventilation at day 14	day 14	Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation.

Secondary Outcome Measures

Name	Time	Method
Survival without needs of ventilator utilization at day 14	14 days	Survival without needs of ventilator utilization (including non-invasive ventilation and Optiflow) at day 14
Cumulative incidence of oxygen supply independency at 14 and 28 days	14 and 28 days	Cumulative incidence of oxygen supply independency
WHO progression scale at day 7 and 14	day 7 and day 14	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
Overall survival at 14, 28, 60 and 90 days	14, 28, 60 and 90 days	Overall survival
Survival without needs of mechanical ventilation at day 1	day 1	Survival without needs of mechanical ventilation at day 1. 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 discharge alive at 14 and 28 days	14 and 28 days	Cumulative incidence of discharge alive

Trial Locations

Locations (1)

CH Andrée Rosemon; 🇬🇫 Cayenne, French Guiana