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

NCT02845843 | Completed Phase 2 DMC

• 1 other identifier: KingAbdullahIMRC
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

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.

Conditions

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 90-day mortality

  90-day

Secondary Outcomes (10)

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

  28 days

• RT-PCR cycle threshold value in the lower respiratory samples

  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

  Days 0, 3, 7, 14, 21 and 28

• ICU-free days

  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

  Up to one year from enrollment

Study Arms (2)

Combination of Lopinavir /Ritonavir and IntErferon Beta 1B

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Combination of Lopinavir /Ritonavir and Interferon beta-1b DRUG

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

Combination of Lopinavir /Ritonavir and IntErferon Beta 1B

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• King Abdullah International Medical Research Center: lead

Study Sites (2)

Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs

Riyadh, 11426, Saudi Arabia

Location

King Abdullah International Medical Research Center

Riyadh, 22490, Saudi Arabia

Location

Related Publications (4)

• 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.

  PMID: 36307462 DERIVED

• 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.

  PMID: 33026741 DERIVED

• 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.

  PMID: 31900204 DERIVED

• 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.

  PMID: 29382391 DERIVED

MeSH Terms

Interventions

Ritonavir; Interferon beta-1b

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: July 27, 2016
• Study Start: July 1, 2016
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: May 20, 2020

Record last verified: 2020-05

Locations

SA (2)