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

• ClinicalTrials.gov Identifier: NCT04276688
• Recruitment Status: Completed
• First Posted: February 19, 2020
• Last Update Posted: April 15, 2020
• Sponsor: The University of Hong Kong
• Collaborator: Hospital Authority, Hong Kong
• Information provided by (Responsible Party): The University of Hong Kong

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 (Clinical Trial)
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: open-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: February 10, 2020
• Actual Primary Completion Date: March 30, 2020
• Actual Study Completion Date: March 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 [ Time Frame: Up to 1 month ]
   Time to negative NPS 2019-n-CoV RT-PCR

Secondary Outcome Measures :

1. Time to negative saliva [ Time Frame: Up to 1 month ]
   Time to negative saliva 2019-n-CoV RT-PCR
2. Time to clinical improvement [ Time Frame: Up to 1 month ]
   Time to NEWS of 0
3. Hospitalisation [ Time Frame: Up to 1 month ]
   Length of hospitalisation
4. Mortality [ Time Frame: Up to 1 month ]
   30-day mortality
5. Immune reaction [ Time Frame: up to 1 month ]
   Cytokine/ chemokine changes
6. Adverse events [ Time Frame: up to 1 month ]
   Adverse events during treatment
7. Time to negative all clinical specimens [ Time Frame: up to 1 month ]
   Time to negative NPS, saliva, urine and stool 2019-n-CoV RT-PCR

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Hong Kong

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moschen AR. IBD in the time of corona - vigilance for immune-mediated diseases. Nat Rev Gastroenterol Hepatol. 2020 Sep;17(9):529-530. doi: 10.1038/s41575-020-0333-5. Review.

Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, Ng YY, Lo J, Chan J, Tam AR, Shum HP, Chan V, Wu AK, Sin KM, Leung WS, Law WL, Lung DC, Sin S, Yeung P, Yip CC, Zhang RR, Fung AY, Yan EY, Leung KH, Ip JD, Chu AW, Chan WM, Ng AC, Lee R, Fung K, Yeung A, Wu TC, Chan JW, Yan WW, Chan WM, Chan JF, Lie AK, Tsang OT, Cheng VC, Que TL, Lau CS, Chan KH, To KK, Yuen KY. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10.

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

Individual Participant Data (IPD) Sharing Statement:

• 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:

Infection; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Interferons; Ritonavir; Ribavirin; Lopinavir; Interferon-beta; Interferon beta-1b; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antimetabolites; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic