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

Novel Coronavirus Infection Clinical Trial

Official title:

An Open-label Randomized Controlled Trial on Lopinavir/ Ritonavir, Ribavirin and Interferon Beta 1b Combination Versus Lopinavir/ Ritonavir Alone, as Treatment for 2019 Novel Coronavirus Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04276688
• Other study ID #: UW-20-074
• Status: Completed
• Phase: Phase 2
• Start date: February 10, 2020
• Est. completion date: March 31, 2020

Study information

• Verified date: April 2020
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: March 31, 2020
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• Infection
• Novel Coronavirus Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• Lopinavir/ritonavir
400mg/100mg twice daily for 14 days
• Ribavirin
400mg twice daily for 14 days
• Interferon Beta-1B
0.25mg subcutaneous injection alternate day for 3 days

Locations

Country	Name	City	State
Hong Kong	University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Hospital Authority, Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

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