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MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

Trial Profile

MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 11 Mar 2019

At a glance

  • Drugs Interferon beta-1b (Primary) ; Lopinavir/ritonavir (Primary)
  • Indications Middle East respiratory syndrome coronavirus
  • Focus Therapeutic Use
  • Acronyms MIRACLE
  • Most Recent Events

    • 06 Mar 2019 Planned End Date changed from 1 Jul 2018 to 1 Dec 2020.
    • 06 Mar 2019 Planned primary completion date changed from 1 Jul 2018 to 1 Dec 2020.
    • 02 Nov 2017 Planned number of patients changed from 80 to 194.

Trial Overview

Purpose

This is a placebo-controlled clinical trial to assess the feasibility, efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with Middle East respiratory syndrome-coronavirus (MERS-CoV).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

Primary Endpoints

90-day mortality

safety_issue: Yes
time_frame: 90-day

Other Endpoints

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 3 consecutive samples are negative or reaching a maximum of 90 days

Sequential organ failure assessment (SOFA) scores

time_frame: Days 1, 3, 5, 7, 14, and 28

Length of stay in ICU

time_frame: Up to one year from enrollment

Length of stay in hospital

time_frame: Up to one year from enrollment

Duration of mechanical ventilation

time_frame: Up to one year from enrollment

Hospital-acquired infections as assessed by the NHSN 2016 definitions

description: Infections will be reported as per the NHSN 2016 definitions, as number of events per devise day or ICU day as appropriate.
time_frame: Up to one year from enrollment

Serial chest radiograph findings

time_frame: 28 day

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 [1]

Diseases Treated

Indication Qualifiers Patient Segments
Middle East respiratory syndrome coronavirus treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 194

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Inclusion criteria at eligibility assessment 1. Adult (defined as ≥18 years of age); 2. Laboratory confirmation of MERS-CoV infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and 3. 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).

Patient Exclusion Criteria

at eligibility assessment 1. Suicidal ideation based on history (contraindication to interferon (IFN)-β1b); 2. 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; 3. Elevated alanine aminotransferase (ALT) >5 fold the upper limit in the hospital's laboratory; 4. Use of medications that are contraindicated with lopinavir/ritonavir and that cannot be replaced or stopped during the study period, such as CYP3A inhibitors; 5. Pregnancy - eligible and consenting female participants in childbearing age will be tested for pregnancy before enrollment in the study; 6. Known HIV infection, because of concerns about the development of resistance to lopinavir/ritonavir if used without combination with other anti-HIV drugs; or 7. Patient likely to be transferred to a non-participating hospital within 72 hours.

Trial Details

Identifiers

Identifier Owner
NCT02845843 ClinicalTrials.gov: US National Institutes of Health
KingAbdullahIMRC -

Trial Dates

  • Initiation Dates

    Planned : 01 Jul 2016

    Actual : 01 Jul 2016

  • Primary Completion Dates

    Planned : 01 Dec 2020

  • End Dates

    Planned : 01 Dec 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised; sequential
  • Phase of Trial Phase II/III
  • Location Saudi Arabia
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
Interferon beta-1bPrimary Drug Subcutaneous Injection
Lopinavir/ritonavirPrimary Drug Oral Tablet

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

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)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Yaseen Arabi, MD
+966-11-8011111 Ext: 18855 yaseenarabi@yahoo.com
show details
-
Yaseen Arabi, MD, FCCP, FCCM
966-11-8011111 18899
+966-11-8011111 Ext: 18855
arabi@ngha.med.sa
yaseenarabi@yahoo.com
show details
King Abdullah International Medical Research Center Saudi-Arabia
Yaseen M Arabi, MD
+966(11)8011111 18855 yaseenarabi@yahoo.com
show details
Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs Saudi-Arabia

Centres

Centre Name Location Trial Centre Country
-
-
-
Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs Riyadh Saudi-Arabia
King Abdullah International Medical Research Center Riyadh Saudi-Arabia

Trial History

Event Date Event Type Comment
11 Mar 2019 Other trial event Last checked against the ClinicalTrials.gov record. Updated 11 Mar 2019
06 Mar 2019 Completion date Planned End Date changed from 1 Jul 2018 to 1 Dec 2020. Updated 11 Mar 2019
06 Mar 2019 Other trial event Planned primary completion date changed from 1 Jul 2018 to 1 Dec 2020. Updated 11 Mar 2019
13 Nov 2018 Other trial event According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified Nov 2016). Updated 13 Nov 2018
30 Jan 2018 Other trial event According trial design published in the trials,the first interim analysis will be conducted when the total subject with 90 days of follow-up reaches 34 subjects (17 per group) Updated 27 Mar 2019
30 Jan 2018 Other trial event According to trial design published in Trials,enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018 Updated 27 Mar 2019
30 Jan 2018 Other trial event Trial design published in the Trials Updated 27 Mar 2019
02 Nov 2017 Other trial event Planned number of patients changed from 80 to 194. Updated 09 Nov 2017
28 Nov 2016 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 01 Dec 2016
30 Jul 2016 New trial record New trial record Updated 30 Jul 2016

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, et al. 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;19(1):81.

    PubMed | CrossRef Fulltext
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