the Investigation Into Beneficial Effects of High-dose Interferon Beta 1-a, Compared to Low-dose Interferon Beta 1-a in Moderate to Severe Covid-19

Study Overview
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Brief Summary
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The present study is a randomized clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

Detailed Description
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According to previous studies, IFN-β has strong antiviral activity and also has an acceptable safety profile. Based on possible therapeutic effects, we decided to lead an Investigation into Beneficial Effects of high-dose Interferon Beta 1a, Compared to low-dose Interferon Beta 1a (the base therapeutic regimen) in Moderate to Severe COVID-19. Previous studies demonstrate that IFN-β 1a could be used against some coronaviruses including avium infectious, bronchitis virus, murine hepatitis virus, and SARS- CoV because they are susceptible in vitro or in vivo. In a current study, the efficacy of IFN-β 1a in COVID-19 patients were evaluated, and they found than IFN-β 1a reduced the disease symptoms. The present study is a randomized clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran.

Official Title
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the Investigation Into Beneficial Effects of High-dose Interferon Beta 1-a, Compared to Low-dose Interferon Beta 1-a in Moderate to Severe Covid-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: High dose Interferon-beta 1a
* Drug: Lopinavir/Ritonavir
* Drug: Low dose Interferon-beta 1a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) at least one of the following: radiation contactless body temperature ≥37.5, cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. Time of onset of the symptoms should be acute (Days ≤ 14) NEWS2 ≥ 1 on admission (National Early Warning Score 2) Exclusion Criteria: Refusal to participate expressed by patient or legally authorized representative if they are present Patients using drugs with potential interaction with Lopinavir/Ritonavir or Interferon-β 1a Pregnant or lactating women. History of alcohol or drug addiction in the past 5 years. Blood ALT/AST levels > 5 times the upper limit of normal on laboratory results. The patients who were intubated less than one hours after admission to the hospital

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1<br>Lopinavir /Ritonavir +high dose Interferon-β 1a | Drug: High dose Interferon-beta 1a<br>* High dose IFN-β1a (Recigen) (Subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6)<br>Drug: Lopinavir/Ritonavir<br>* Lopinavir/Ritonavir (Kaletra) [IFN-β1a group] (400mg/100 mg twice a day for 10 days<br>|
| Experimental: Arm2<br>Lopinavir /Ritonavir + Low dose Interferon-β 1a | Drug: Lopinavir/Ritonavir<br>* Lopinavir/Ritonavir (Kaletra) [IFN-β1a group] (400mg/100 mg twice a day for 10 days<br>Drug: Low dose Interferon-beta 1a<br>* Low doseIFN-β1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement | Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first. | From date of randomization until 14 days later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | If the patient dies, we have reached an outcome | From date of randomization until 14 days later | 
| SpO2 Improvement | Pulse-oxymetry | Days 1, 2, 3, 4, 5, 6, 7 and 14 | 
| Incidence of new mechanical ventilation use |  | From date of randomization until 14 days later | 
| Duration of hospitalization |  | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days | 
| Cumulative incidence of serious adverse events | With the incidence of any serious adverse effects, the outcome has happened | Days 1, 2, 3, 4, 5, 6, 7 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Interferons, Ritonavir, Lopinavir, Interferon-beta, Antiviral Agents, Anti-Infective Agents, Immunologic Factors