• Yaseen M Arabi, Ayed Y Asiri, Abdullah M Assiri, Hanan H Balkhy, Ali Al Bshabshe, Majed Al Jeraisy, Yasser Mandourah, Mohamed H A Azzam, Abdulhadi M Bin Eshaq, Sameera Al Johani, Shmeylan Al Harbi, Hani A A Jokhdar, Ahmad M Deeb, Ziad A Memish, Jesna Jose, Sameeh Ghazal, Sarah Al Faraj, Ghaleb A Al Mekhlafi, Nisreen M Sherbeeni, Fatehi E Elzein, Fahad Al-Hameed, Asim Al Saedi, Naif K Alharbi, Robert A Fowler, Frederick G Hayden, Abdulaziz Al-Dawood, Mohamed Abdelzaher, Wail Bajhmom, Badriah M AlMutairi, Mohamed A Hussein, Adel Alothman, and Saudi Critical Care Trials Group.
• From the Intensive Care Department (Y.M.A., A.A.-D.) and the Departments of Infection Prevention and Control (H.H.B.), Pathology and Laboratory Medicine (S.A.J.), Pharmaceutical Care (S.A.H.), and Medicine (A.A.), King Abdulaziz Medical City, Ministry of National Guard Health Affairs, the College of Medicine (Y.M.A., S.A.J., A.A.-D., A.A.) and the College of Pharmacy (M.A.J., S.A.H.), King Saud bin Abdulaziz University for Health Sciences, Prince Mohammed bin Abdulaziz Hospital (A.Y.A., Z.A.M., S.G., S.A.F.), Infection Prevention and Control, Preventive Health (A.M.A.), and Deputyship for Public Health (H.A.A.J.), Ministry of Health, Clinical Trials Services (M.A.J., A.M.D., B.M.A.) and the Departments of Biostatistics and Informatics (J.J., M.A.H.) and Infectious Disease Research (N.K.A.), King Abdullah International Medical Research Center, the Military Medical Services, Ministry of Defense (Y.M.), the Department of Intensive Care Services (G.A.A.M.), and the Infectious Diseases Division (N.M.S., F.E.E.), Prince Sultan Military Medical City, and the College of Medicine, Alfaisal University (Z.A.M.), Riyadh, the Department of Critical Care Medicine, King Khalid University, Aseer Central Hospital, Abha (A.A.B.), Medical Services (M.H.A.A.) and the Department of Critical Care Medicine (M.A.), King Abdullah Medical Complex, the Health Directorate, Ministry of Health (M.H.A.A.), and the Internal Medicine Department, King Fahad General Hospital, Ministry of Health (W.B.), the Intensive Care Department (F.A.-H.) and the Department of Infection Prevention and Control (A.A.S.), Ministry of National Guard Health Affairs, and the College of Medicine and King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (F.A.-H., A.A.S.), Jeddah, and the Intensive Care Department, King Khalid Hospital, Najran (A.M.B.E.) - all in Saudi Arabia; the World Health Organization, Geneva (H.H.B.); the Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta (Z.A.M.); the Departments of Critical Care Medicine and Medicine, Sunnybrook Hospital, and the Institute of Health Policy Management and Evaluation, University of Toronto, Toronto (R.A.F.); and the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.).
• N. Engl. J. Med. 2020 Oct 22; 383 (17): 1645-1656.

BackgroundWhether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear.MethodsWe conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results.ResultsA total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group.ConclusionsA combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).Copyright © 2020 Massachusetts Medical Society.

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