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

The University of Hong Kong127 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

127

Conditions

Novel Coronavirus Infection

Interventions

Lopinavir/ritonavirDRUG

400mg/100mg twice daily for 14 days

RibavirinDRUG

400mg twice daily for 14 days

Interferon Beta-1BDRUG

0.25mg subcutaneous injection alternate day for 3 days

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Outcomes

Primary Outcomes

Time to negative NPS

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

Time frame: Up to 1 month

Secondary Outcomes

Time to negative saliva

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

Time frame: Up to 1 month

Time to clinical improvement

Time to NEWS of 0

Time frame: Up to 1 month

Hospitalisation

Length of hospitalisation

Time frame: Up to 1 month

Mortality

30-day mortality

Time frame: Up to 1 month

Immune reaction

Cytokine/ chemokine changes

Time frame: up to 1 month

Adverse events

Adverse events during treatment

Time frame: up to 1 month

Time to negative all clinical specimens

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

Time frame: up to 1 month

Data from ClinicalTrials.gov

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