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CompletedNCT02845843MIRACLEUpdated May 20, 2020

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

A Phase 2/3 interventional study of Combination of Lopinavir /Ritonavir and Interferon beta-1b and Placebo in Middle East Respiratory Syndrome Coronavirus (MERS-CoV), sponsored by King Abdullah International Medical Research Center. Completed at 2 sites in Saudi Arabia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-05-20.

Sponsored by King Abdullah International Medical Research Center · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
95
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Keywords

  • Middle East Respiratory Syndrome Coronavirus
  • MERS-CoV
  • Clinical trial
  • Lopinavir
  • Ritonavir
  • Interferon beta
03

In context

Lead sponsor

King Abdullah International Medical Research Center is the lead sponsor of 46 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  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).

Exclusion criteria

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.
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
95 participants (actual)

Study arms

  • 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

  • Placebo comparator
    Placebo

    Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

    Drug: Placebo

Interventions

  • DrugCombination of Lopinavir /Ritonavir and Interferon beta-1b

    Drug pages: Lopinavir · Ritonavir · 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

  • DrugPlacebo

    Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

06

What researchers measure

Primary outcomes

  1. 90-day mortality

    Time frame: 90-day

Secondary outcomes

  1. Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)

    Time frame: 28 days

  2. 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

  3. Sequential organ failure assessment (SOFA) scores

    Time frame: Days 0, 3, 7, 14, 21 and 28

  4. 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

  5. Length of stay in hospital

    Time frame: Up to one year from enrollment

  6. Number of Patients with Adverse drug reactions related to the treatment

    Time frame: From enrollment to 28 day

  7. Karnofsky Performance Scale

    Time frame: 90-day

  8. ICU mortality

    Time frame: Up to one year from enrollment

  9. Hospital mortality

    Time frame: Up to one year from enrollment

  10. 28-day mortality

    Time frame: 28-day

07

Study locations

2 sites
  • Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs
    Riyadh, 11426, Saudi Arabia
  • King Abdullah International Medical Research Center
    Riyadh, 22490, Saudi Arabia
08

References and documents

Publications

  • 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. PubMed 36307462 ↗
  • 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. PubMed 33026741 ↗
  • 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. PubMed 31900204 ↗
  • 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. PubMed 29382391 ↗

Individual participant data

Plan to share: Undecided

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jul 2016 to primary completion in May 2020, 46 months.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 20, 2016
First posted
Jul 27, 2016
StartActual
Jul 2016
Primary completionActual
May 2020
CompletionActual
May 2020
Last update
May 20, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 20, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02845843
Lead sponsor
King Abdullah International Medical Research Center
Responsible party
Sponsor
First posted
Jul 27, 2016
Start date
Jul 2016
Primary completion
May 2020
Completion
May 2020
Last update
May 20, 2020

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Studies of the drugs tested here: Lopinavir · Ritonavir · Interferon beta-1b

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King Abdullah International Medical Research Center

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