Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact email@example.com.
Timely Administration of Tocilizumab Improves Survival of Hospitalized COVID-19 Patients
20 Pages Posted: 27 Apr 2021More...
Background: Accumulating evidence points to an overactive immune response in Covid-19 disease and potential clinical benefit of the interleukin-6 inhibitor tocilizumab. We assessed the efficacy of early tocilizumab treatment for hospitalized patients in a randomized phase II study.
Methods: Patients admitted to the general ward with proven Covid-19 and in need of supplemental oxygen were randomly assigned to receive standard of care with or without intravenous tocilizumab 8 mg/kg (maximal 800 mg). A second dose of tocilizumab was permitted if hypoxia persisted after 8 hrs. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α=0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days.
Findings: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR)=0.62 (90% CI 0.39-0.98; p=0.086). 21% of patients were admitted to the ICU in each arm (p=0.89). The median stay in the ICU was 16 days (IQR 8-30) in the standard arm versus 9 days (IQR 5-16) in the tocilizumab arm (p=0.025). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p=0.042).
Interpretation: Various studies have suggested a beneficial effect of tocilizumab in the treatment of COVID-19. This randomized phase II study, which met its primary endpoint, confirms these observations and demonstrates a clinically meaningful efficacy when given early in the disease course in hospitalized patients who need oxygen support, even when concomitantly treated with dexamethasone.
Trial Registration: The trial was designed as a prospective randomized (1:1) open label phase II trial and was registered in the Netherlands Trial register (https://www.trialregister.nl/trial/8504).
Funding Statement: Academic study, funded by participating hospitals. Roche supplied tocilizumab.
Declaration of Interests: None to declare.
Ethics Approval Statement: The trial was approved by the relevant medical ethical committee and was performed in accordance with Good Clinical Practice guidelines and the Helsinki Declaration.
Suggested Citation: Suggested Citation