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

NCT04476979 | Completed Phase 2 DMC

• 2 other identifiers: APHP200375-TOCIDEX2020-001246-18
• Study Type: interventional
• Target: 453
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• WHO progression scale at day 7 and 14

  day 7 and day 14

• Overall survival at 14, 28, 60 and 90 days

  14, 28, 60 and 90 days

• Cumulative incidence of discharge alive at 14 and 28 days

  14 and 28 days

• Survival without needs of mechanical ventilation at day 1

  day 1

• Cumulative incidence of oxygen supply independency at 14 and 28 days

  14 and 28 days

Study Arms (2)

Dexamethasone

ACTIVE COMPARATOR

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 + Tocilizumab

EXPERIMENTAL

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; Drug: Dexamethasone

Interventions

Tocilizumab DRUG

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

Dexamethasone DRUG

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; Dexamethasone + Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

CH Andrée Rosemon

Cayenne, French Guiana

Location

Related Publications (1)

• 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.

  PMID: 35350097 RESULT

MeSH Terms

Conditions

Coronavirus Infections; Severe Acute Respiratory Syndrome; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Interventions

tocilizumab; Dexamethasone

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 20, 2020
• Study Start: July 16, 2020
• Primary Completion: June 1, 2021
• Study Completion: August 11, 2021
• Last Updated: May 31, 2024

Record last verified: 2024-05

Locations

FR (1)