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

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.

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.