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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04276688
Recruitment Status : Completed
First Posted : February 19, 2020
Last Update Posted : April 15, 2020
Sponsor:
Collaborator:
Hospital Authority, Hong Kong
Information provided by (Responsible Party):
The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE February 11, 2020
First Posted Date  ICMJE February 19, 2020
Last Update Posted Date April 15, 2020
Actual Study Start Date  ICMJE February 10, 2020
Actual Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2020)
Time to negative NPS [ Time Frame: Up to 1 month ]
Time to negative NPS 2019-n-CoV RT-PCR
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2020)
  • Time to negative saliva [ Time Frame: Up to 1 month ]
    Time to negative saliva 2019-n-CoV RT-PCR
  • Time to clinical improvement [ Time Frame: Up to 1 month ]
    Time to NEWS of 0
  • Hospitalisation [ Time Frame: Up to 1 month ]
    Length of hospitalisation
  • Mortality [ Time Frame: Up to 1 month ]
    30-day mortality
  • Immune reaction [ Time Frame: up to 1 month ]
    Cytokine/ chemokine changes
  • Adverse events [ Time Frame: up to 1 month ]
    Adverse events during treatment
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2020)
  • Time to negative saliva [ Time Frame: Up to 1 month ]
    Time to negative saliva 2019-n-CoV RT-PCR
  • Time to clinical improvement [ Time Frame: Up to 1 month ]
    Time to NEWS of 0
  • Hospitalisation [ Time Frame: Up to 1 month ]
    Length of hospitalisation
  • Mortality [ Time Frame: Up to 1 month ]
    30-day mortality
  • Immune reaction [ Time Frame: up to 1 month ]
    Cytokine/ chemokine changes
  • Adverse events [ Time Frame: up to 1 month ]
    Adverse events during treatment
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lopinavir/ Ritonavir, Ribavirin and IFN-beta Combination for nCoV Treatment
Official Title  ICMJE 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
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
open-label randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Novel Coronavirus Infection
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Study group
    triple combination
    Interventions:
    • Drug: Lopinavir/ritonavir
    • Drug: Ribavirin
    • Drug: Interferon Beta-1B
  • Active Comparator: Control group
    single
    Intervention: Drug: Lopinavir/ritonavir
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 13, 2020)
127
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2020)
70
Actual Study Completion Date  ICMJE March 31, 2020
Actual Primary Completion Date March 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04276688
Other Study ID Numbers  ICMJE UW-20-074
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Hospital Authority, Hong Kong
Investigators  ICMJE
Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP