“Background: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.
Methods: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3…
Results: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality …
Trial Procedures: … Patients in the remdesivir group received a loading dose on day 1 (200 mg in adults, and adjusted for body weight in pediatric patients), followed by a daily maintenance dose (100 mg in adults) starting on day 2 and continuing for 9 to 13 days, depending on viral load…”
Note: For comparison, the standard, FDA-recommended dosing regimen of remdesivir for treatment of COVID-19 for hospitalized adults and children is as follows:
- RDV 200 mg IVa on Day 1, then RDV 100 mg IV on Days 2–5
- For patients who do not show clinical improvement after 5 days of therapy, treatment may be extended to up to 10 days.
From Table 2. Comparison of Death at 28 Days According to Treatment Group (see image below):
- 53.1% of all remdesivir patients died (93/175)
- 85.3% of remdesivir patients with high viral load died (64/75)
- 29.0% of remdesivir patients with low viral load died (29/100)
Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.
© 2019 Massachusetts Medical Society. All rights reserved. NEJM Group content is protected by copyright. While many NEJM Group content items such as articles, figures, tables, videos, and podcasts are free online, NEJM Group content is for personal, non-commercial use in accordance with copyright law. Reuse of Content Within a Thesis or Dissertation Content (full-text or portions thereof) may be used in print and electronic versions of a dissertation or thesis without formal permission from the Massachusetts Medical Society (MMS), Publisher of the New England Journal of Medicine. The following credit line must be printed along with the copyrighted material: Reproduced with permission from (scientific reference citation), Copyright Massachusetts Medical Society. Source: https://www.nejm.org/about-nejm/permissions