MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b (MIRACLE)

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ClinicalTrials.gov Identifier: NCT02845843

Recruitment Status : Completed

First Posted : July 27, 2016

Last Update Posted : May 20, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

King Abdullah International Medical Research Center

Study Description

Brief Summary:

This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.

Condition or disease	Intervention/treatment	Phase
Middle East Respiratory Syndrome Coronavirus (MERS-CoV)	Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b Drug: Placebo	Phase 2 Phase 3

Detailed Description:

The aim of this study is to investigate the efficacy and safety of lopinavir /ritonavir and recombinant Interferon beta-1b combination given with optimal supportive care compared to placebo with optimal supportive care for patients with laboratory-confirmed MERS-CoV infection requiring hospital admission.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	95 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	This is a 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 (n=34). The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size.
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial
Actual Study Start Date :	July 2016
Actual Primary Completion Date :	May 2020
Actual Study Completion Date :	May 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Interferon Interferon beta Interferon beta-1b Ritonavir Lopinavir

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Combination of Lopinavir /Ritonavir and IntErferon Beta 1B Lopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days	Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b Lopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days
Placebo Comparator: Placebo Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding	Drug: Placebo Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

Outcome Measures

Primary Outcome Measures :

90-day mortality [ Time Frame: 90-day ]

Secondary Outcome Measures :

Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors) [ Time Frame: 28 days ]
RT-PCR cycle threshold value in the lower respiratory samples [ Time Frame: At randomization and every 3 days afterwards, until 2 consecutive samples are negative or reaching a maximum of 90 days ]
Sequential organ failure assessment (SOFA) scores [ Time Frame: Days 0, 3, 7, 14, 21 and 28 ]
ICU-free days [ Time Frame: Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment ]
Length of stay in hospital [ Time Frame: Up to one year from enrollment ]
Number of Patients with Adverse drug reactions related to the treatment [ Time Frame: From enrollment to 28 day ]
Karnofsky Performance Scale [ Time Frame: 90-day ]
ICU mortality [ Time Frame: Up to one year from enrollment ]
Hospital mortality [ Time Frame: Up to one year from enrollment ]
28-day mortality [ Time Frame: 28-day ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria at eligibility assessment

Adult (defined as ≥18 years of age);
Laboratory confirmation of MERS-CoV infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
New organ dysfunction that is judged to related to MERS including: hypoxia defined as requirement of supplemental oxygen to maintain oxygen saturations >90%, hypotension (systolic blood pressure<90 mmHg) or need for vasopressor/inotropic medication, renal impairment (increase of creatinine by 50% from baseline, glomerular filtration rate reduction by >25% from baseline or urine output of <0.5 ml/kg for 6 hours - Risk stage by RIFLE criteria), neurologic (reduction of Glasgow Coma Scale by 2 or more, i.e. 13 or lower of 15 points), thrombocytopenia (<150,000 platelets/mm3) or gastrointestinal symptoms that requires hospitalization (e.g. severe nausea, vomiting, diarrhea or/and abdominal pain).

Exclusion criteria at eligibility assessment

Suicidal ideation based on history (contraindication to interferon (IFN)-β1b);
Known allergy or hypersensitivity reaction to lopinavir/ritonavir or to recombinant IFN-β1b, including, but not limited to, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria or angioedema;
Elevated alanine aminotransferase (ALT) >5 fold the upper limit in the hospital's laboratory;
Use of medications that are contraindicated with lopinavir/ritonavir and that cannot be replaced or stopped during the study period, such as CYP3A inhibitors;
Pregnancy - eligible and consenting female participants in childbearing age will be tested for pregnancy before enrollment in the study;
Known HIV infection, because of concerns about the development of resistance to lopinavir/ritonavir if used without combination with other anti-HIV drugs; or
Patient likely to be transferred to a non-participating hospital within 72 hours.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02845843

Locations

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Saudi Arabia
Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs
Riyadh, Saudi Arabia, 11426
King Abdullah International Medical Research Center
Riyadh, Saudi Arabia, 22490

Sponsors and Collaborators

King Abdullah International Medical Research Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Arabi YM, Asiri AY, Assiri AM, Abdullah ML, Aljami HA, Balkhy HH, Al Jeraisy M, Mandourah Y, AlJohani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Hayden FG, Fowler RA, AlMutairi BM, Al-Dawood A, Alharbi NK. Heterogeneity of treatment effect of interferon-beta1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels. Sci Rep. 2022 Oct 28;12(1):18186. doi: 10.1038/s41598-022-22742-8.

Arabi YM, Asiri AY, Assiri AM, Balkhy HH, Al Bshabshe A, Al Jeraisy M, Mandourah Y, Azzam MHA, Bin Eshaq AM, Al Johani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Al-Hameed F, Al Saedi A, Alharbi NK, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, AlMutairi BM, Hussein MA, Alothman A; Saudi Critical Care Trials Group. Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome. N Engl J Med. 2020 Oct 22;383(17):1645-1656. doi: 10.1056/NEJMoa2015294. Epub 2020 Oct 7.

Arabi YM, Asiri AY, Assiri AM, Aziz Jokhdar HA, Alothman A, Balkhy HH, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Memish ZA, Ghazal S, Al Faraj S, Al-Hameed F, AlSaedi A, Mandourah Y, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Almotairi A, Al Bshabshe A, Kharaba A, Jose J, Al Harthy A, Al Sulaiman M, Mady A, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, Hussein MA; and the Saudi Critical Care Trials group. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-beta1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials. 2020 Jan 3;21(1):8. doi: 10.1186/s13063-019-3846-x.

Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Assiri AM, Al-Hameed F, AlSaedi A, Mandourah Y, Almekhlafi GA, Sherbeeni NM, Elzein FE, Memon J, Taha Y, Almotairi A, Maghrabi KA, Qushmaq I, Al Bshabshe A, Kharaba A, Shalhoub S, Jose J, Fowler RA, Hayden FG, Hussein MA; And the MIRACLE trial group. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018 Jan 30;19(1):81. doi: 10.1186/s13063-017-2427-0.

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Responsible Party:	King Abdullah International Medical Research Center
ClinicalTrials.gov Identifier:	NCT02845843
Other Study ID Numbers:	KingAbdullahIMRC
First Posted:	July 27, 2016 Key Record Dates
Last Update Posted:	May 20, 2020
Last Verified:	May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by King Abdullah International Medical Research Center:


Middle East Respiratory Syndrome Coronavirus MERS-CoV Clinical trial	Lopinavir Ritonavir Interferon beta

Additional relevant MeSH terms:

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Coronavirus Infections Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Virus Diseases Interferons Ritonavir Lopinavir Interferon-beta Interferon beta-1b Antineoplastic Agents Antiviral Agents	Anti-Infective Agents HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic

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