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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 2

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

Treatments: Drug: Tocilizumab; Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT04476979

2020-001246-18 (EudraCT Number)

APHP200375-TOCIDEX

Details and patient eligibility

About

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

Enrollment: 453 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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453 participants in 2 patient groups

Dexamethasone

Active Comparator group

Description:

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)

Treatment:

Drug: Dexamethasone

Dexamethasone + Tocilizumab

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Tocilizumab