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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 453
• Phase: Phase 2

Contacts and Locations

Study Locations

• French Guiana
  • Cayenne, French Guiana
    • CH Andrée Rosemon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall survival at 14, 28, 60 and 90 days	Overall survival	14, 28, 60 and 90 days
Cumulative incidence of discharge alive at 14 and 28 days	Cumulative incidence of discharge alive	14 and 28 days
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
Cumulative incidence of oxygen supply independency at 14 and 28 days	Cumulative incidence of oxygen supply independency	14 and 28 days
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Hermine O, Mariette X, Porcher R, Djossou F, Nguyen Y, Arlet JB, Savale L, Diehl JL, Georgin-Lavialle S, Cadranel J, Pialoux G, Lacombe K, Mekinian A, Gros H, Lescure X, Ghosn J, Coupez E, Grapin K, Rapp C, Michel M, Lecapitaine AL, Michot JM, Costedoat-Chalumeau N, Nguyen LBL, Semerano L, Raffi F, Aguillar C, Rouzaud C, Gottenberg JE, Hansmann Y, Bienvenu B, London J, Fantchou FS, Ackermann F, Gros A, Morel A, Gambier N, Sene D, Megarbane B, Azoulay E, Bureau S, Dougados M, Emmerich J, Fartoukh M, Guidet B, Humbert M, Mahevas M, Pene F, Schlemmer F, Pourcher-Martinez V, Tibi A, Baron G, Perrodeau E, Baron S, Steg G, Yazdapanah Y, Simon T, Resche-Rigon M, Tharaux PL, Ravaud P. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group. EClinicalMedicine. 2022 Mar 25;46:101362. doi: 10.1016/j.eclinm.2022.101362. eCollection 2022 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 31, 2024
• Last Update Submitted That Met QC Criteria: May 29, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Severe Acute Respiratory Syndrome; Coronavirus Infections; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; RNA Virus Infections; Coronaviridae Infections; Nidovirales Infections; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: APHP200375-TOCIDEX; 2020-001246-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No