Double Therapy With IFN-beta 1b and Hydroxychloroquine

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Prijava / prijava

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StanjeDokončano

Sponzorji

The University of Hong Kong

KLINIČNO PRESKUŠANJE: NCT04350281

BioSeek: nct04350281

Ključne besede

Povzetek

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.

Opis

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.

Datumi

Nazadnje preverjeno:	06/30/2020
Prvič predloženo:	04/12/2020
Predviden vpis oddan:	04/12/2020
Prvič objavljeno:	04/16/2020
Zadnja posodobitev oddana:	07/26/2020
Zadnja posodobitev objavljena:	07/27/2020
Dejanski datum začetka študija:	04/08/2020
Predvideni datum primarnega zaključka:	06/30/2020
Predvideni datum zaključka študije:	07/06/2020

Stanje ali bolezen

COVID

Intervencija / zdravljenje

Drug: Treatment group

Drug: Hydroxychloroquine

Faza

Faza 2

Skupine rok

Roka	Intervencija / zdravljenje
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: Treatment group Daily subcutaneous injection of interferon β-1b 1mL (0.25mg; 8 million IU) consecutively on day 1 to day 3
Active Comparator: Control group Hydroxychloroquine 800mg on day 1, then 400mg daily for 2 days plus standard care alone.

Merila upravičenosti

Starost, primerna za študij	18 Years Za 18 Years
Spol, upravičen do študija	All
Sprejema zdrave prostovoljce	Da
Merila	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.

Izid

Primarni izidni ukrepi

1. Time to negative NPS viral load [4 weeks]

Time to negative NPS SARS-CoV-2 viral RT-PCR

Ukrepi sekundarnega rezultata

1. Time to NEWS 0 [4 weeks]

Time to complete allevation of symptoms as defined by NEWS of 0 maintained for 24 hours

2. Length of Hospitalisation [4 weeks]

Days of hospital stay

3. Time to negative viral load in all clinical samples [4 weeks]

Time to negative SARS-CoV-2 viral RT-PCR in all clinical samples

4. Adverse events [4 weeks]

Treatment related adverse events

5. Mortality [30 days]

30-day mortality

6. Inflammatory markers changes [4 weeks from diagnosis]

Cytokine/ chemokine

Double Therapy With IFN-beta 1b and Hydroxychloroquine

Ključne besede

covid-19

pneumonia

coronavirus infections

sclerosis

mrzlica

atrofija

kašelj

respiratory insufficiency

multipla skleroza

mialgija

protivirusno zdravilo