Trial EU-CTR 2020-002037-15
Publication Sancho-Lopez A, Infect Dis Ther, 2021 (published paper)
Dates: 2020-08-04 to 2021-03-23
Funding: Private (Biomedical Research Foundation of the Puerta de Hierro Majadahonda University
Hospital; Sanofi (drug donation))
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Spain Follow-up duration (days): 28 | |
| Inclusion criteria | Patients at least 18 years of age and hospitalized due to COVID-19 confirmed by positive RT-PCR or antigen test; Presented with pneumonia defined by the radiographic evidence of pulmonary infiltrates by imaging, or rales/crackles on examination, and required standard oxygen supplement due to SpO2 ≤ 94% on room air; Time from symptom onset to inclusion must be at least 7 days; Patients must present elevation of IL-6 more than 40 pg/mL, or d-dimer more than 1.0 mcg/ml, or at least two of the following analytical inflammatory parameters: elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, or lymphopenia. |
| Exclusion criteria | Patients with high oxygen requirements (including face mask with reservoir bag, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation); Had been on treatment with CS for more than 1 day; Were admitted to the intensive care unit (ICU); Pregnant or lactating; Had allergy or hypersensitivity to sarilumab or CS; Had received immunosuppressive monoclonal antibody therapy within the past 5 months; AST/ALT values more than 10 x ULN; Neutropenia (less than 0.5 x 109/L); Severe thrombocytopenia (less than 50 x 109/L); Sepsis caused by an alternative pathogen; Diverticulitis with risk of perforation; Ongoing infectious dermatitis. |
| Interventions | |
| Treatment
Sarilumab 200 mg IV infusion for 1 hour (if body weight < 75 kg) 400 mg IV infusion for 1 hour (if body weight >= 75 kg) |
|
| Control
Standard care ( / ) Definition of Standard care: Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days as part of the SOC background medication. SOC also included antibiotic agents, antiviral agents, steroid boluses, vasopressor support, and anticoagulants that were provided at the discretion of the investigators. | |
| Participants | |
| Randomized 201 participants (n1=99 / n2= 102) | |
| Characteristics of participants N=201 Mean age : 60 141 males Severity : Mild: n=0 / Moderate: n=201/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Proportion of patients progressing to severe respiratory failure (Brescia-COVID Scale ≥2), ICU admission, or death. | |
| In the report Proportion of patients progressing to severe respiratory failure (Brescia-COVID equal or higher than 3, defined by the need of high frequency nasal ventilation, CPAP or noninvasive ventilation or mechanical ventilation), admission to the ICU, or death | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
| 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 published article, the study registry and supplementary file were used in data extraction and risk of bias assessment. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499-518 was also available.
The registry primary outcome does not reflect the reported primary outcome. Outcomes from the registry were specified at 15 days as a timepoint vs the outcomes in report are reported at 28 days as a timepoint. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. This study was updated on November 18th, 2021 with data from the published journal report. |