Trial NCT04476979
Publication Hermine O, EClinicalMedicine, 2021 (published paper)
Dates: 2020-07-24 to 2021-05-18
Funding: Public/non profit (Ministry of Health, Programme Hospitalier de Recherche Clinique; Fondation de l’Assistance Publique – Hôpitaux de Paris, Alliance Tous Unis Contre le Virus; Fédération pour la Recherche Médicale)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / France, French Guyana Follow-up duration (days): 90 | |
| Inclusion criteria | Confirmed SARS CoV-2 infection (positive PCR and/or typical chest CT-scan); moderate and severe pneumopathy requiring oxygen (>3 L/min) but without ventilation support (NIV), high flow or MV; WHO class 5 according to the WHO 10 points-Clinical Progression Scale (CPS) for COVID-19 pneumopathy |
| Exclusion criteria | Known hypersensitivity to TCZ; pregnancy; current documented bacterial infection; absolute neutrophil count (ANC) less 1.0 x 109 /L or less; platelets (PLT) less 50 G /L; ALAT more 5N |
| Interventions | |
| Treatment
Tocilizumab + Dexamethasone TCZ: 8 mg/kg once-off intravenously; then 400 mg intravenously at day 3 if not 50% reduction in oxygen requirement; Dex: tapering dose - 10 mg once a day for 5 days, then 5 mg/day for 5 days, then 2.5 mg/day for 5 days, orally. |
|
| Control
Dexamethasone ( / ) | |
| Participants | |
| Randomized 453 participants (n1=226 / n2= 227) | |
| Characteristics of participants N=453 Mean age : NR 305 males Severity : Mild: n=0 / Moderate: n=450/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Survival without needs of invasive ventilation at day 14 | |
| In the report Survival without the need for invasive ventilation at day 14 | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated
|
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment |
In addition to the pre-print article, the prospective registry and the statistical analysis plan shared with other CORIMUNO trials were used in data extraction and assessment of risk of bias. No protocol was available. Supplementary materials referred to in the pre-print article were not available at time of extraction. There were no substantive differences in the primary and secondary clinical outcomes between the article and the registry. Safety outcomes reported in the article were not included in the registry. The trial was terminated after a planned interim analysis due to low event rates requiring an increased sample size and a reduction in recruitment.
Of note, data for the outcome, time to WHO score 7 and above (mechanical ventilation or death) is reported as a median posterior hazard ratio adjusted for age and centre with 90% credible interval (Bayesian analysis). This study was updated on April 25th 2022 with data from the published report. |