As of 1 July 2020, more than 10 million people been confirmed to have infected by SARS-CoV-2, resulting in more than 500,000 deaths. No specific antiviral treatment for the SARS-CoV-2 is currently available, but existing medication could be repurposed. The investigators therefore propose to conduct an open-label randomized controlled trial on a short course of interferon β-1b and ribavirin combination treatment for patients hospitalized for COVID-19 infection.
The novel coronavirus (SARS-CoV-2), is a single-stranded RNA coronavirus. The virus was first
isolated from patients presented with pneumonia in Wuhan in December 2019. It is believed
that the virus first emerged from patients working in the Wuhan Seafood Market which also
sold contaminated wild animals, consumed as a local delicacy. Sequences of the Wuhan
betacoronavirus show similarities to betacoronaviruses found in bats, sharing a common
ancestor with the 2003 SARS coronavirus (SARS-CoV).
The SARS-CoV-2 has since spread from China to the rest of the world. As of 1 July 2020, more
than 10 million people been confirmed to have infected by SARS-CoV-2, resulting in more than
500,000 deaths. No specific antiviral treatment for the SARS-CoV-2 is currently available,
but existing medication could be repurposed.
Previously, the investigators have demonstrated that interferon beta-1b, commonly used in the
treatment of multiple sclerosis and lopinavir/ ritonavir, also demonstrated to improve the
outcome of MERS-CoV infection in a non-human primate model of common marmoset. More recently,
the investigators have demonstrated that the triple combination of interferon β-1b,
lopinavir/ ritonavir and ribavirin was significantly more effective in alleviating symptoms
and respiratory SARS-CoV-2 viral load than lopinavir/ ritonavir with ribavirin or lopinavir/
ritonavir alone, suggesting that interferon β-1b might be the most potent antiviral among the
three and lopinavir/ ritonavir is associated with relatively more side effects including
diarrhoea and cardiac arrhythmia.
Therefore, the investigators propose to conduct an open-label randomized controlled trial on
a short course of interferon β-1b and ribavirin combination treatment for patients
hospitalized for COVID-19 infection.
Patients will be randomly assigned to one of the two groups: the Treatment group: a 5-day
course of subcutaneous injection of interferon β-1b 2mL (16 million IU) consecutively and
oral ribavirin 400mg twice daily, or the Control group: supportive care alone (1:1).
For patients randomized to the Control group, if the nasopharyngeal swab (NPS) or throat
saliva (TS) viral load is still detectable on day 3, the patients will receive the same
treatment as in the Treatment group from day 4 to day 8.
Drug: Interferon beta-1b
5-day course of daily subcutaneous injection of interferon β-1b 16 million IU
Drug: Ribavirin
5-day course of oral ribavirin 400mg twice daily
Inclusion Criteria:
1. Recruited subjects include all adult patients ≥18 years hospitalized for virologic
confirmed SARS-CoV-2 infection.
2. All subjects give written informed consent. For patients who are critically ill,
requiring ICU, ventilation or confused, informed consent will be obtained from spouse,
next-of-kin or legal guardians.
3. 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 taking medication that will potentially interact with l interferon beta-1b or
ribavirin
4. Pregnant or lactation women
5. Patients with known history of severe depression
6. 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.
7. To participate in an unrelated trial during the current clinical trial. Nevertheless,
the patients have the right to withdraw from the current clinical trial to join
another clinical trial.
8. Have a history of alcohol or drug abuse in the last 5 years.
9. Have any condition that the investigator believes may interfere with successful
completion of the study.
The University of Hong Kong, Queen Mary Hospital
Hong Kong, Hong Kong
Investigator: Ivan FN Hung, MD FRCP
Contact: 22554049
ivanhung@hku.hk
Investigator:
Ivan FN Hung, MD FRCP
22554049
ivanhung@hku.hk
Kelvin KW To, MD FRCPath
22552584
kelvinto@hku.hk
Ivan FN Hung, MD FRCP, Principal Investigator
The University of Hong Kong