Double Therapy With IFN-beta 1b and Hydroxychloroquine
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04350281|
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : April 17, 2020
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. Sequences of the Wuhan betacoronavirus show similarities to betacoronaviruses found in bats, sharing a common ancestor with the 2003 SARS coronavirus (SARS-CoV) and the bat coronavirus HKU9, a virus found in fruit bats. Similar to SARS-CoV, it is a member of Beta-CoV lineage B. Five genomes of the novel coronavirus have been initially isolated and reported including BetaCoV/Wuhan/IVDC-HB-01/2019, BetaCoV/Wuhan/IVDC-HB-04/2020, BetaCoV/Wuhan/IVDC-HB-05/2019, BetaCoV/Wuhan/WIV04/2019, and BetaCoV/Wuhan/IPBCAMS-WH-01/2019 from the China CDC.
The SARS-CoV-2 has since spread from China to the rest of the world. As of 5 April 2020, more than 1.05 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.
Genetic sequencing demonstrated similarity of the SARS-CoV-2 to the SARS-CoV and MERS CoV.2 We expect patients infected with the SARS-CoV-2 will also present similarly with initial upper respiratory tract symptoms including fever, cough, sputum, myalgia and shortness or breath. More severe cases might complicate with pneumonia and required ventilatory or ECMO support. According to our previous studies in 2003 on patients hospitalized for severe SARS-CoV, the viral load peaked between day 7 from symptoms onset and coincided with clinical deterioration of pneumonia and respiratory failure, with majority of the patients required intensive care support. Higher viral load isolated from different human system also correlated with worsened SARS manifestation and complications.
Previously, we 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.
A non-randomized trial has also suggested that a combination of hydroxychloroquine and azithromycin might be effective in suppressing SARS-CoV-2 viral load in patients, despite in-vitro activity was only found in hydroxychloroquine.
Therefore, we propose to conduct an open-label randomized controlled trial on a short course of interferon β-1b and hydroxychloroquine combination treatment for patients hospitalized for COVID-19 infection.
|Condition or disease||Intervention/treatment||Phase|
|COVID||Drug: Interferon Beta-1B Drug: Hydroxychloroquine||Phase 2|
This is a prospective open-label randomised controlled trial among adult patients hospitalised after April 2020 for virologically confirmed SARS-CoV-2 infection.
Patients will be randomly assigned to either the treatment group: a 3-day course of 3 doses of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care, or the control group: a 3-day course of hydroxycholoroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone (1:1).
For the control group, if the day 4 nasopharyngeal swab (NPS) viral load remains positive, then patients will receive another 3 days of subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) and hydroxychloroquine 400mg daily.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Randomized Controlled Trial on Interferon β-1b and Hydroxychloroquine Combination Versus Hydroxychloroquine Alone, as Treatment for COVID-19 Infection|
|Actual Study Start Date :||April 9, 2020|
|Estimated Primary Completion Date :||March 31, 2022|
|Estimated Study Completion Date :||July 31, 2022|
Active Comparator: Treatment group
Subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3 and hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care
Drug: Interferon Beta-1B
Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days
Active Comparator: Control group
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.
Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days
- Time to negative NPS viral load [ Time Frame: 4 weeks ]Time to negative NPS SARS-CoV-2 viral RT-PCR
- Time to NEWS 0 [ Time Frame: 4 weeks ]Time to complete allevation of symptoms as defined by NEWS of 0 maintained for 24 hours
- Length of Hospitalisation [ Time Frame: 4 weeks ]Days of hospital stay
- Time to negative viral load in all clinical samples [ Time Frame: 4 weeks ]Time to negative SARS-CoV-2 viral RT-PCR in all clinical samples
- Adverse events [ Time Frame: 4 weeks ]Treatment related adverse events
- Mortality [ Time Frame: 30 days ]30-day mortality
- Inflammatory markers changes [ Time Frame: 4 weeks from diagnosis ]Cytokine/ chemokine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04350281
|Contact: Ivan FN Hung, MD FRCPemail@example.com|
|Contact: Kelvin KW To, MD FRCPathfirstname.lastname@example.org|
|The University of Hong Kong, Queen Mary Hospital||Recruiting|
|Hong Kong, Hong Kong, 852|
|Contact: Ivan FN Hung, MD FRCP 22554049 email@example.com|
|Contact: Kelvin KW To, MD FRCPath firstname.lastname@example.org|
|Principal Investigator: Ivan FN Hung, MD FRCP|
|Sub-Investigator: Kelvin To, MD MRCP|
|Principal Investigator:||Ivan FN Hung, MD FRCP||The University of Hong Kong|