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

King Abdullah International Medical Research Center

Status and phase: Completed; Phase 3; Phase 2

Conditions: Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Treatments: Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02845843

KingAbdullahIMRC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 95 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

95 participants in 2 patient groups, including a placebo group

Combination of Lopinavir /Ritonavir and IntErferon Beta 1B

Experimental group

Description:

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

Treatment:

Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo