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

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Clinical Trial

— MIRACLE  

Official title:

MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02845843
• Other study ID #: KingAbdullahIMRC
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2016
• Est. completion date: May 2020

Study information

• Verified date: May 2020
• Source: King Abdullah International Medical Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: May 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)-ß1b);

2. Known allergy or hypersensitivity reaction to lopinavir/ritonavir or to recombinant IFN-ß1b, 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.

Related Conditions & MeSH terms

• Coronavirus Infections
• Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Intervention

Drug:
• 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
• Placebo
Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

Locations

Country	Name	City	State
Saudi Arabia	Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs	Riyadh
Saudi Arabia	King Abdullah International Medical Research Center	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
King Abdullah International Medical Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day mortality		90-day
Secondary	Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)		28 days
Secondary	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
Secondary	Sequential organ failure assessment (SOFA) scores		Days 0, 3, 7, 14, 21 and 28
Secondary	ICU-free days		Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment
Secondary	Length of stay in hospital		Up to one year from enrollment
Secondary	Number of Patients with Adverse drug reactions related to the treatment		From enrollment to 28 day
Secondary	Karnofsky Performance Scale		90-day
Secondary	ICU mortality		Up to one year from enrollment
Secondary	Hospital mortality		Up to one year from enrollment
Secondary	28-day mortality		28-day