TOCIDEX: Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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) |
Drug: 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)
|
| Experimental: Dexamethasone + 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 |
Drug: Tocilizumab
Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
Drug: 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)
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Cumulative incidence of discharge alive at 14 and 28 days [14 and 28 days]
Cumulative incidence of discharge alive
- 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 oxygen supply independency at 14 and 28 days [14 and 28 days]
Cumulative incidence of oxygen supply independency
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients included in the CORIMUNO-19 cohort
-
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,
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Active tuberculosis or disseminated strongyloidiasis
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Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
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Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
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Haemoglobin level: no limitation
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Platelets (PLT) < 50 G /L
-
SGOT or SGPT > 5N
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CH Andrée Rosemon | Cayenne | French Guiana |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
- Institut National de la Santé Et de la Recherche Médicale, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP200375-TOCIDEX
- 2020-001246-18