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

Study Overview
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Brief Summary
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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
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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: Time to negative saliva 2019-n-CoV coronavirus viral RT-PCR Time to clinical improvement of NEWS2 (National Early Warning Score 2) of 0 maintained for 24 hours Length of hospitalisation Adverse events during treatment 30-day mortality Cytokine/ chemokine changes

Official Title
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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

Conditions
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Novel Coronavirus Infection

Intervention / Treatment
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* Drug: Lopinavir/ritonavir
* Drug: Ribavirin
* Drug: Interferon Beta-1B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recruited subjects include all adult patients ≥18 years hospitalised for virologically confirmed 2019-n-CoV infection. NEWS of ≥1 upon recruitment 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 Symptom duration ≤10 days All subjects give written informed consent. 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: Inability to comprehend and to follow all required study procedures. Allergy or severe reactions to the study drugs Patients with known prolonged QT or PR interval, second- or third-degree heart block, or ventricular cardiac arrhythmias, including torsade de pointes Patients taking medication that will potentially interact with lopinavir/ ritonavir, ribavirin or interferon-beta1b Patients with known history of severe depression Pregnant or lactation women Inability to comprehend and to follow all required study procedures 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. Have a history of alcohol or drug abuse in the last 5 years. Have any condition that the investigator believes may interfere with successful completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: open-label randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to negative NPS | Time to negative NPS 2019-n-CoV RT-PCR | Up to 1 month | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nCoV, lopinavir/ ritonavir, IFN-beta