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

Respiratory Tract Infections Clinical Trial

— TOCIDEX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04476979
• Other study ID #: APHP200375-TOCIDEX
• Secondary ID: 2020-001246-18
• Status: Completed
• Phase: Phase 2
• Start date: July 16, 2020
• Est. completion date: August 11, 2021

Study information

• Verified date: May 2022
• 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 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 453
• Est. completion date: August 11, 2021
• Est. primary completion date: June 1, 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 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

Related Conditions & MeSH terms

• Communicable Diseases
• Coronaviridae Infections
• Coronavirus Infection
• Coronavirus Infections
• Infections
• Nidovirales Infections
• Respiratory Tract Disease
• Respiratory Tract Diseases
• Respiratory Tract Infections
• RNA Virus Infections
• SARS (Severe Acute Respiratory Syndrome)
• Severe Acute Respiratory Syndrome
• Virus Diseases

Intervention

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
• 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)

Locations

Country	Name	City	State
French Guiana	CH Andrée Rosemon	Cayenne

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

French Guiana, 

Outcome

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