Lopinavir/ Ritonavir, Ribavirin and IFN-beta Combination for nCoV Treatment

Phase 2

Completed

• Conditions: Novel Coronavirus Infection
• Interventions: Drug: Lopinavir/ritonavir; Drug: Ribavirin; Drug: Interferon Beta-1B

• Registration Number: NCT04276688
• Lead Sponsor: The University of Hong Kong

Brief Summary

A combination of lopinavir/ ritonavir, ribavirin and interferon beta-1b will expedite the recovery, suppress the viral load, shorten hospitalisation and reduce mortality in patients with 2019-n-CoV infection compared with to lopinavir/ ritonavir

Detailed Description

Hypothesis A combination of lopinavir/ ritonavir, ribavirin and interferon beta-1b will expedite the recovery, suppress the viral load, shorten hospitalisation and reduce mortality in patients with 2019-n-CoV infection compared with to lopinavir/ ritonavir alone

Primary objective: To evaluate the safety and efficacy in mortality reduction with a combination of lopinavir/ ritonavir, ribavirin and interferon beta-1b in the treatment of patient hospitalised for 2019-n-CoV infection and compare this to lopinavir/ ritonavir alone

Subject/patient definition: Recruited subjects include adult patients ≥18 years of age, admitted to the HA Hospitals from February 2020 onwards, with laboratory confirmed 2019-n-CoV infection. All subjects give written informed consent. Subjects must be available to complete the study and comply with study procedures.

Study design: This is a prospective open-label randomised controlled trial among adult patients hospitalised after February 2020 for virologically confirmed 2019-n-CoV infection. Patients will be randomly assigned to either a 14-day course of lopinavir/ ritonavir 400mg/100mg twice daily, ribavirin 400mg bd and zero to three doses of subcutaneous injection of interferon beta-1b 1mL (0.25mg; 8 million IU) on day 1, 3 and 5 (depending on day of admission from symptoms onset) plus standard care, or a 14-day course of lopinavir/ ritonavir 400mg/100mg twice daily plus standard care alone (2:1).

Intervention/study article: lopinavir/ ritonavir, ribavirin and interferon beta-1b

Primary outcome: Time to negative nasopharyngeal swab (NPS) 2019-n-CoV coronavirus viral RT-PCR

Secondary outcome:

1. Time to negative saliva 2019-n-CoV coronavirus viral RT-PCR

2. Time to clinical improvement of NEWS2 (National Early Warning Score 2) of 0 maintained for 24 hours

3. Length of hospitalisation

4. Adverse events during treatment

5. 30-day mortality

6. Cytokine/ chemokine changes

Study Timeline

• Study Start: 2020-02-10
• Study First Submitted: 2020-02-11
• Study First Submitted QC: 2020-02-17
• Study First Posted: 2020-02-19
• Primary Completion: 2020-03-30
• Study Completion: 2020-03-31
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-13
• Last Update Posted: 2020-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

Inclusion Criteria

1. Recruited subjects include all adult patients ≥18 years hospitalised for virologically confirmed 2019-n-CoV infection.
2. NEWS of ≥1 upon recruitment
3. Auditory temperature ≥38°C with at least one of the following symptoms (cough, sputum production, sore-throat, nasal discharge, myalgia, headache or fatigue) upon admission
4. Symptom duration ≤10 days
5. All subjects give written informed consent.
6. Subjects must be available to complete the study and comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response.

Exclusion Criteria

1. Inability to comprehend and to follow all required study procedures.
2. Allergy or severe reactions to the study drugs
3. Patients with known prolonged QT or PR interval, second- or third-degree heart block, or ventricular cardiac arrhythmias, including torsade de pointes
4. Patients taking medication that will potentially interact with lopinavir/ ritonavir, ribavirin or interferon-beta1b
5. Patients with known history of severe depression
6. Pregnant or lactation women
7. Inability to comprehend and to follow all required study procedures
8. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
9. Have a history of alcohol or drug abuse in the last 5 years.
10. Have any condition that the investigator believes may interfere with successful completion of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study group	Interferon Beta-1B	triple combination
Control group	Lopinavir/ritonavir	single
Study group	Lopinavir/ritonavir	triple combination
Study group	Ribavirin	triple combination

Primary Outcome Measures

Name	Time	Method
Time to negative NPS	Up to 1 month	Time to negative NPS 2019-n-CoV RT-PCR

Secondary Outcome Measures

Name	Time	Method
Time to negative saliva	Up to 1 month	Time to negative saliva 2019-n-CoV RT-PCR
Time to clinical improvement	Up to 1 month	Time to NEWS of 0
Hospitalisation	Up to 1 month	Length of hospitalisation
Mortality	Up to 1 month	30-day mortality
Immune reaction	up to 1 month	Cytokine/ chemokine changes
Adverse events	up to 1 month	Adverse events during treatment
Time to negative all clinical specimens	up to 1 month	Time to negative NPS, saliva, urine and stool 2019-n-CoV RT-PCR

Trial Locations

Locations (1)

University of Hong Kong, Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong