Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Conditions
Keywords
Middle East Respiratory Syndrome Coronavirus, MERS-CoV, Clinical trial, Lopinavir, Ritonavir, Interferon beta
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.
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.
Interventions
DRUGCombination 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
DRUGPlacebo
Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding
Sponsors
King Abdullah International Medical Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 90-day mortality | 90-day |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors) | 28 days |
| Karnofsky Performance Scale | 90-day |
| ICU mortality | Up to one year from enrollment |
| Hospital mortality | Up to one year from enrollment |
| 28-day mortality | 28-day |
| Number of Patients with Adverse drug reactions related to the treatment | From enrollment to 28 day |
Countries
Saudi Arabia
Outcome results
None listed