Trial Trial NL8504
Publication Rutgers A, SSRN, 2021 (preprint)
Dates: 2020-04-06 to 2021-01-12
Funding: Mixed (Participating hospitals; Roche (drug supplier))
Conflict of interest: No
Methods | |
RCT Blinding: Unblinded | |
Location :
Multicenter / The Netherlands Follow-up duration (days): 90 | |
Inclusion criteria | 18 years or older; capable of providing informed consent; SARS-CoV-2 infection confirmed by nasopharyngeal swab polymerase chain reaction; admitted to a ward; have at least one of the following signs compatible with hyperinflammation: 1) a need for supplemental oxygen (inspired by the ASTCT consensus grade 2 for CRS, generally matching a saturation < 94%) and/or 2) ferritin >2000ug/l or a doubling of serum ferritin in 20-48 hrs. |
Exclusion criteria | Pregnancy; allergy to tocilizumab. |
Interventions | |
Treatment
Tocilizumab 8 mg/kg IV infusion once-off, maximum 800 mg. A second infusion could be administered 8 after the first |
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Control
Standard care ( / ) Definition of Standard care: Standard of care. The majority of patients (88%) received dexamethasone as a concomitant treatment. All other concomitants were permitted, including remdesivir and hydroxychloroquine. | |
Participants | |
Randomized 354 participants (n1=174 / n2= 180) | |
Characteristics of participants N=354 Mean age : NR 237 males Severity : Mild: n=0 / Moderate: n=257/ Severe: n=82 Critical: n=3 | |
Primary outcome | |
In the register 30-day mortality (from randomization) | |
In the report Mortality after randomization, assessed as a time-to-event endpoint | |
Documents available |
Protocol NR Statistical plan NR Data-sharing stated
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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 |
Low |
General comment | In addition to the pre-print article, the prospective trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The study achieved it target sample size.There is no change from the trial registration in the intervention and control treatments. The registry primary outcome does reflect the reported primary outcome. Some outcomes in the registry (normalization of HRCT, seroconversion 14 days after randomization) were not reported in the pre-print paper. Some outcomes are reported in the paper, but were not pre-specified in the trial registry (for example time to death, time to WHO score 7 and above). Considered an interim analysis since only 30-day outcomes are reported. A 3-month endpoint is included in the registry, which reports study status as recruitment completed with follow up continuing. |