Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial
Top Cited Papers
Open Access
- 30 January 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Trials
- Vol. 19 (1), 1-13
- https://doi.org/10.1186/s13063-017-2427-0
Abstract
Background: It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-beta 1b (IFN-beta 1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-beta 1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion: This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018.Funding Information
- King Abdullah International Medical Research Center (RC15/142)
This publication has 37 references indexed in Scilit:
- MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatmentJournal of General Virology, 2013
- Human Cell Tropism and Innate Immune System Interactions of Human Respiratory Coronavirus EMC Compared to Those of Severe Acute Respiratory Syndrome CoronavirusJournal of Virology, 2013
- Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirinScientific Reports, 2013
- Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensusGut, 2012
- Conducting Research in Disease OutbreaksPLoS Neglected Tropical Diseases, 2009
- Tolerability and safety profile of 12- to 28-week treatment with interferon beta-1b 250 and 500 µg QOD in patients with relapsing-remitting multiple sclerosis: A multicenter, randomized, double-blind, parallel-group pilot studyClinical Therapeutics, 2008
- Interferon beta-1b (Betaseron®/Betaferon®) is well tolerated at a dose of 500 mg: interferon dose escalation assessment of safety (IDEAS)Multiple Sclerosis Journal, 2006
- Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findingsThorax, 2004
- Modification of the sample size and the schedule of interim analyses in survival trials based on data inspectionsStatistics in Medicine, 2001
- Uniform Requirements for Manuscripts Submitted to Biomedical JournalsThe New England Journal of Medicine, 1997