Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial

被引：218

作者：

Arabi, Yaseen M. ^{[1
,2
,27
]}

Alothman, Adel ^{[1
,3
]}

Balkhy, Hanan H. ^{[1
,4
]}

Al-Dawood, Abdulaziz ^{[1
,2
]}

AlJohani, Sameera ^{[1
,5
]}

Al Harbi, Shmeylan ^{[6
,7
]}

Kojan, Suleiman ^{[1
,3
]}

Al Jeraisy, Majed ^{[6
,7
]}

Deeb, Ahmad M. ^{[1
,2
]}

Assiri, Abdullah M. ^{[8
]}

Al-Hameed, Fahad ^{[9
,10
]}

AlSaedi, Asim ^{[9
,11
]}

Mandourah, Yasser ^{[12
]}

Almekhlafi, Ghaleb A. ^{[12
]}

Sherbeeni, Nisreen Murad ^{[13
]}

Elzein, Fatehi Elnour ^{[13
]}

Memon, Javed ^{[14
]}

Taha, Yusri ^{[15
]}

Almotairi, Abdullah ^{[16
]}

Maghrabi, Khalid A. ^{[17
]}

Qushmaq, Ismael ^{[18
]}

Al Bshabshe, Ali ^{[19
]}

Kharaba, Ayman ^{[20
]}

Shalhoub, Sarah ^{[21
]}

Jose, Jesna ^{[22
]}

Fowler, Robert A. ^{[23
,24
,25
]}

Hayden, Frederick G. ^{[26
]}

Hussein, Mohamed A. ^{[22
]}

机构：

[1] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Coll Med, Riyadh, Saudi Arabia

[2] King Abdul Aziz Med City, Intens Care Dept, Riyadh, Saudi Arabia

[3] King Abdul Aziz Med City, Dept Med, Riyadh, Saudi Arabia

[4] King Abdul Aziz Med City, Dept Infect Prevent & Control, Riyadh, Saudi Arabia

[5] King Abdul Aziz Med City, Dept Pathol & Lab Med, Riyadh, Saudi Arabia

[6] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Coll Pharm, Riyadh, Saudi Arabia

[7] King Abdul Aziz Med City, Pharmaceut Care Dept, Riyadh, Saudi Arabia

[8] Minist Hlth, Infect Prevent & Control, Riyadh, Saudi Arabia

[9] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Coll Med, Jeddah, Saudi Arabia

[10] King Abdul Aziz Med City, Intens Care Dept, Jeddah, Saudi Arabia

[11] King Abdul Aziz Med City, Dept Infect Prevent & Control, Jeddah, Saudi Arabia

[12] Prince Sultan Mil Med City, Dept Intens Care Serv, Riyadh, Saudi Arabia

[13] Prince Sultan Mil Med City, Infect Dis Div, Riyadh, Saudi Arabia

[14] King Abdulaziz Hosp, Dept Med, Intens Care Sect, Alahsa, Saudi Arabia

[15] King Abdulaziz Hosp, Dept Med, Alahsa, Saudi Arabia

[16] King Fahad Med City, Dept Crit Care Med, Riyadh, Saudi Arabia

[17] King Faisal Specialist Hosp & Res, Dept Crit Care Med, Riyadh, Saudi Arabia

[18] King Faisal Specialist Hosp & Res, Dept Med, Jeddah, Saudi Arabia

[19] King Khalid Univ, Aseer Cent Hosp, Dept Crit Care Med, Abha, Saudi Arabia

[20] Ohoud Hosp, King Fahad Hosp, Dept Critical Care, Al Madinah, Al Monawara, Saudi Arabia

[21] King Fahad Armed Forces Hosp, Dept Med, Jeddah, Saudi Arabia

[22] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Dept Biostat & Bioinformat, Riyadh, Saudi Arabia

[23] Univ Toronto, Inst Hlth Policy Management & Evaluat, AIP PED HSE HQ, AMR Infect Control & Publicat, Toronto, ON, Canada

[24] Sunnybrook Med Ctr, Dept Crit Care Med, 2075 Bayview Ave,Room D478, Toronto, ON, Canada

[25] Sunnybrook Med Ctr, Dept Med, 2075 Bayview Ave,Room D478, Toronto, ON, Canada

[26] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA

[27] Univ Oxford, Intt Severe Acute Resp & Emerging Infect Consorti, Old Rd Campus,Roosevelt Dr, Oxford OX3 7FZ, England

来源：

TRIALS | 2018年 / 19卷

关键词：

Coronavirus; MERS; Antiviral; Saudi Arabia; Clinical trial; Lopinavir/ritonavir; Interferon-beta; 1b; SYNDROME CORONAVIRUS INFECTION; 500; MU-G; INTERNATIONAL CONSENSUS; MULTIPLE-SCLEROSIS; BROAD-SPECTRUM; RIBAVIRIN; LOPINAVIR/RITONAVIR; THERAPY; SAFETY; INTERFERON-ALPHA-2B;

D O I：

10.1186/s13063-017-2427-0

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页数：13

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