Double Therapy With IFN-beta 1b and Hydroxychloroquine

NCT ID: NCT04350281

Last Updated: 2020-07-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-09

Study Completion Date

2020-07-07

Brief Summary

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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, 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.

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, the investigators 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.

Detailed Description

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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.

Conditions

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COVID

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Interferon Beta-1B

Intervention Type DRUG

Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3

Hydroxychloroquine

Intervention Type DRUG

Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days

Control group

Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.

Group Type ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type DRUG

Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days

Interventions

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Interferon Beta-1B

Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3

Intervention Type DRUG

Hydroxychloroquine

Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days

Intervention Type DRUG

Eligibility Criteria

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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 with known prolonged QTc syndrome, ventricular cardiac arrhythmias, including torsade de pointes, second or third degree heart block, QTc interval \>480ms
4. Patients taking medication that will potentially interact with l interferon beta-1b or hydroxychloroquine
5. Patients with known underlying retinopathy
6. Patients with G6PD deficiency
7. Patients with known history of severe depression
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.
9. 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.
10. Have a history of alcohol or drug abuse in the last 5 years.
11. Have any condition that the investigator believes may interfere with successful completion of the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Ivan FN Hung MD

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ivan FN Hung, MD FRCP

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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The University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Countries

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Hong Kong

Other Identifiers

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UW 20-211

Identifier Type: -

Identifier Source: org_study_id

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