Clinical trial NCT04476979: Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19
Official title: Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Infection
SARS (Severe Acute Respiratory Syndrome)
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2020-07-20
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Survival without needs of invasive ventilation at day 14
timeFrame: day 14
Secondary outcomes:
measure: WHO progression scale at day 7 and 14
timeFrame: day 7 and day 14
measure: Overall survival at 14, 28, 60 and 90 days
timeFrame: 14, 28, 60 and 90 days
measure: Cumulative incidence of discharge alive at 14 and 28 days
timeFrame: 14 and 28 days
measure: Survival without needs of mechanical ventilation at day 1
timeFrame: day 1
measure: Cumulative incidence of oxygen supply independency at 14 and 28 days
timeFrame: 14 and 28 days
measure: Survival without needs of ventilator utilization at day 14
timeFrame: 14 days
Other outcomes:
Locations:
city: Cayenne
country: French Guiana
facility: CH Andrée Rosemon
Study officials:
References:
citation: 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.