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Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.
Trials. 2018 Jan 30; 19(1):81.T

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-β1b (IFN-β1b) 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-β1b 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.

TRIAL REGISTRATION

ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Authors+Show Affiliations

College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. arabi@ngha.med.sa. Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. arabi@ngha.med.sa. International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. arabi@ngha.med.sa.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Department of Infection Prevention and Control, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.Infection Prevention and Control, Ministry of Health, Riyadh, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia. Intensive Care Department, King Abdulaziz Medical City, Jeddah, Saudi Arabia.College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia. Department of Infection Prevention and Control, King Abdulaziz Medical City, Jeddah, Saudi Arabia.Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Infectious Diseases Division, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Infectious Diseases Division, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Intensive Care Section, Department of Medicine, King Abdulaziz Hospital, Alahsa, Saudi Arabia.Department of Medicine, King Abdulaziz Hospital, Alahsa, Saudi Arabia.Department of Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.Department of Critical Care Medicine, King Faisal Specialist Hospital and Research, Riyadh, Saudi Arabia.Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.Department of Critical Care Medicine, King Khalid University, Aseer Central Hospital, Abha, Saudi Arabia.Department of Critical Care, King Fahad Hospital, Ohoud Hospital, Al-Madinah Al-Monawarah, Saudi Arabia.Department of Medicine, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.Department of Biostatistics and Bioinformatics, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.AMR Infection Control and Publications AIP/PED/HSE/HQ, Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada. Department of Critical Care Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, Canada. Department of Medicine, Sunnybrook Hospital, 2075 Bayview Avenue, Room D478, Toronto, ON, Canada.Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA.Department of Biostatistics and Bioinformatics, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.No affiliation info available

Pub Type(s)

Clinical Trial Protocol
Journal Article

Language

eng

PubMed ID

29382391

Citation

Arabi, Yaseen M., et al. "Treatment of Middle East Respiratory Syndrome With a Combination of Lopinavir-ritonavir and Interferon-β1b (MIRACLE Trial): Study Protocol for a Randomized Controlled Trial." Trials, vol. 19, no. 1, 2018, p. 81.
Arabi YM, Alothman A, Balkhy HH, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018;19(1):81.
Arabi, Y. M., Alothman, A., Balkhy, H. H., Al-Dawood, A., AlJohani, S., Al Harbi, S., Kojan, S., Al Jeraisy, M., Deeb, A. M., Assiri, A. M., Al-Hameed, F., AlSaedi, A., Mandourah, Y., Almekhlafi, G. A., Sherbeeni, N. M., Elzein, F. E., Memon, J., Taha, Y., Almotairi, A., ... Hussein, M. A. (2018). Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials, 19(1), 81. https://doi.org/10.1186/s13063-017-2427-0
Arabi YM, et al. Treatment of Middle East Respiratory Syndrome With a Combination of Lopinavir-ritonavir and Interferon-β1b (MIRACLE Trial): Study Protocol for a Randomized Controlled Trial. Trials. 2018 Jan 30;19(1):81. PubMed PMID: 29382391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. AU - Arabi,Yaseen M, AU - Alothman,Adel, AU - Balkhy,Hanan H, AU - Al-Dawood,Abdulaziz, AU - AlJohani,Sameera, AU - Al Harbi,Shmeylan, AU - Kojan,Suleiman, AU - Al Jeraisy,Majed, AU - Deeb,Ahmad M, AU - Assiri,Abdullah M, AU - Al-Hameed,Fahad, AU - AlSaedi,Asim, AU - Mandourah,Yasser, AU - Almekhlafi,Ghaleb A, AU - Sherbeeni,Nisreen Murad, AU - Elzein,Fatehi Elnour, AU - Memon,Javed, AU - Taha,Yusri, AU - Almotairi,Abdullah, AU - Maghrabi,Khalid A, AU - Qushmaq,Ismael, AU - Al Bshabshe,Ali, AU - Kharaba,Ayman, AU - Shalhoub,Sarah, AU - Jose,Jesna, AU - Fowler,Robert A, AU - Hayden,Frederick G, AU - Hussein,Mohamed A, AU - ,, Y1 - 2018/01/30/ PY - 2017/05/08/received PY - 2017/12/20/accepted PY - 2018/2/1/entrez PY - 2018/2/1/pubmed PY - 2019/3/15/medline KW - Antiviral KW - Clinical trial KW - Coronavirus KW - Interferon-β1b KW - Lopinavir/ritonavir KW - MERS KW - Saudi Arabia SP - 81 EP - 81 JF - Trials JO - Trials VL - 19 IS - 1 N2 - 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-β1b (IFN-β1b) 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-β1b 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. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/29382391/Treatment_of_Middle_East_Respiratory_Syndrome_with_a_combination_of_lopinavir_ritonavir_and_interferon_β1b__MIRACLE_trial_:_study_protocol_for_a_randomized_controlled_trial_ L2 - https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2427-0 DB - PRIME DP - Unbound Medicine ER -