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

• Sponsor: The University of Hong Kong (Other)
• Overall Status: Completed
• CT.gov ID: NCT04276688
• Collaborator: Hospital Authority, Hong Kong (Other)
• Enrollment: 127
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.6
• Patients Per Site Per Month: 77.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Novel Coronavirus Infection	Drug: Lopinavir/ritonavir; Drug: Ribavirin; Drug: Interferon Beta-1B	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: open-label randomised controlled trialopen-label randomised controlled trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 10, 2020
• Actual Primary Completion Date: Mar 30, 2020
• Actual Study Completion Date: Mar 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Study group triple combination	Drug: Lopinavir/ritonavir; 400mg/100mg twice daily for 14 days; Drug: Ribavirin; 400mg twice daily for 14 days; Drug: Interferon Beta-1B; 0.25mg subcutaneous injection alternate day for 3 days
Active Comparator: Control group single	Drug: Lopinavir/ritonavir; 400mg/100mg twice daily for 14 days

Outcome Measures

Primary Outcome Measures

1. Time to negative NPS [Up to 1 month]

   Time to negative NPS 2019-n-CoV RT-PCR

Secondary Outcome Measures

1. Time to negative saliva [Up to 1 month]

   Time to negative saliva 2019-n-CoV RT-PCR

2. Time to clinical improvement [Up to 1 month]

   Time to NEWS of 0

3. Hospitalisation [Up to 1 month]

   Length of hospitalisation

4. Mortality [Up to 1 month]

   30-day mortality

5. Immune reaction [up to 1 month]

   Cytokine/ chemokine changes

6. Adverse events [up to 1 month]

   Adverse events during treatment

7. Time to negative all clinical specimens [up to 1 month]

   Time to negative NPS, saliva, urine and stool 2019-n-CoV RT-PCR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Hong Kong, Queen Mary Hospital	Hong Kong		Hong Kong

Sponsors and Collaborators

• The University of Hong Kong
• Hospital Authority, Hong Kong

Investigators

• Principal Investigator: Ivan FN Hung, MD FRCP, The University of Hong Kong

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04276688
• Other Study ID Numbers: UW-20-074
• First Posted: Feb 19, 2020
• Last Update Posted: Apr 15, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by The University of Hong Kong: nCoV; lopinavir/ ritonavir; IFN-beta
• Additional relevant MeSH terms: Infections; Coronavirus Infections; Interferons; Ritonavir; Ribavirin; Lopinavir; Interferon-beta; Interferon beta-1b

Study Results

No Results Posted as of Apr 15, 2020