Interferon Beta 1a in Hospitalized COVID-19 Patients (IB1aIC)

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ClinicalTrials.gov Identifier: NCT04350671

Recruitment Status : Enrolling by invitation

First Posted : April 17, 2020

Last Update Posted : April 20, 2020

Sponsor:

Information provided by (Responsible Party):

Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Shahid Beheshti University of Medical Sciences

Study Description

Brief Summary:

The present study is a randomized, double-blind, placebo-controlled, 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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Interferon Beta-1A Drug: Lopinavir / Ritonavir Drug: Single Dose of Hydroxychloroquine	Phase 4

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Detailed Description:

According to previous studies, IFN-β, amongst IFN-1s, 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 Interferon Beta 1a, Compared to Interferon Beta 1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19. In a 2003 study, SARS was treated with different human interferons and found that IFN-β was 5 to 10 times more effective than other types of interferons and the strongest antiviral drug possible against SARS-CoV.

Chloroquine has been a broadly-utilized anti-malaria agent which back in 2006, had been proved to be a powerful wide-spectrum antiviral. Moreover, Chloroquine has the characteristics of anti-inflammatory and immune-modulatory by inhibiting the production of TNF-α along with IL-6. In the first half of February, Wang et al illustrated puissant inhibition of SARS-CoV-2 by Chloroquine, when taking two 500-mg tablets of it by mouth per day; similar to some clinical studies in China through this outbreak. According to the news briefing of works of Per Gao et al., it was indicated that chloroquine phosphate actually outdo the control treatment in inhibition of pneumonia exacerbation, improving lung imaging findings, and curtailing the disease course. X. Yao et al. evaluated the possible doses of CQ and HCQ to find the optimized dose in treatment of COVID-19. They revealed that while within in-vitro settings Hydroxychloroquine is more potent than chloroquine. As a conclusion, they suggested a 800 mg daily dose of hydroxychloroquine, followed by an overall maintenance dose of 400 mg per day divided in two separate doses, which was three-fold more potent compared to the 500 mg twice daily administration of chloroquine in 5 days. The new study of Gautret et al. published in 16th March, pointed out that hydroxychloroquine was notably effectual in eradicating SARS-CoV-2 from the nasopharynx. Currently the evidence is quite inconclusive about the effectiveness or comparative effectiveness of either HCQ or CQ. Moreover, CQ has recently become scarce and even unavailable for ordering due to a huge demand for it, all because of a significant interest gained as a potential medicinal alternative for the management of COVID-19. In spite of all, the primary experience in China and France is propitious for the potential role of chloroquine, or alternatively hydroxychloroquine, for managing COVID-19.

Lopinavir, classified in the drug group of protease inhibitors, is utilized for the treatment of patients affected prolongedly with HIV-1. The mechanism by which Lopinavir acts is blocking the main protease of SARS-CoV-1, resulting in inhibition of viral replication. Real-world information supporting the treatment of COVID-19 with LPV/r keep coming out. Chu et al. have discovered that LPV/r has an anti-SARS-CoV effect within both in-vitro settings and clinical studies. In disclosed results of Young and colleagues' research on COVID-19 patients in Singapore, 5 cases received LPV/r monotherapy. Among those 5 patients, 3 had decrease in oxygen requirements after treatment, while the other 2 had their conditions worsened to the point of respiratory failure. Other published evaluations from Korea and China made up of a total of 6 patients, show reduced viral load, and clinical improvement after onset of LPV/r treatment. Latterly, Cao and colleagues illustrated the results of comparing twice a day use of LPV/r 400/100 mg to standard care, for treating the pneumonia caused by SARS-CoV-2. This study's upshot, demonstrated no benefit regarding a lopinavir-ritonavir treatment beyond standard care. Considering the currently available data, it is yet to be determined whether LPV/r could significantly affect the status of COVID-19 patients, either as monotherapy or in combination-therapy. Moreover, close monitoring is needed during the administration of this drug, because particularly elevated levels of AST or ALT suggesting the gastrointestinal complications and hepatoxicity may exclude patients with COVID-19 from clinical trials.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	The present study is a randomized, double-blind, placebo-controlled, 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.
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial
Estimated Study Start Date :	April 15, 2020
Estimated Primary Completion Date :	April 20, 2020
Estimated Study Completion Date :	April 24, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Interferon Interferon beta Interferon beta-1a Avonex

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Interferon-β 1a Interferon-β 1a + Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine	Drug: Interferon Beta-1A This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Interferon-β 1a in COVID-19 patients. Drug: Lopinavir / Ritonavir This Drug will be used in all arms as mandated by our governmental guidelines. Drug: Single Dose of Hydroxychloroquine This Drug will be used in all arms as mandated by our governmental guidelines.
Active Comparator: Control Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine	Drug: Lopinavir / Ritonavir This Drug will be used in all arms as mandated by our governmental guidelines. Drug: Single Dose of Hydroxychloroquine This Drug will be used in all arms as mandated by our governmental guidelines.

Arm

Intervention/treatment

Experimental: Interferon-β 1a

Interferon-β 1a + Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine

Drug: Interferon Beta-1A

This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Interferon-β 1a in COVID-19 patients.

Drug: Lopinavir / Ritonavir

This Drug will be used in all arms as mandated by our governmental guidelines.

Drug: Single Dose of Hydroxychloroquine

This Drug will be used in all arms as mandated by our governmental guidelines.

Active Comparator: Control

Lopinavir / Ritonavir + Single Dose of Hydroxychloroquine

Drug: Lopinavir / Ritonavir

This Drug will be used in all arms as mandated by our governmental guidelines.

Drug: Single Dose of Hydroxychloroquine

This Drug will be used in all arms as mandated by our governmental guidelines.

Outcome Measures

Primary Outcome Measures :

Time to clinical improvement [ Time Frame: From date of randomization until 14 days later. ]
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.

Secondary Outcome Measures :

Mortality [ Time Frame: From date of randomization until 14 days later. ]
If the patient dies, we have reached an outcome.
SpO2 Improvement [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7 and 14 ]
Pulse-oxymetry
Incidence of new mechanical ventilation use [ Time Frame: From date of randomization until 14 days later ]
Incidence of new mechanical ventilation use
Duration of hospitalization [ Time Frame: 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. ]
Duration of hospitalization (days)
Cumulative incidence of serious adverse events [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7 and 14. ]
With incidence of any serious adverse effects, the outcome has happened.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	50 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥ 50
COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed).
Tympanic Temperature of ≥37.5 AND at least one of the following: Cough, Sputum production, nasal discharge, myalgia, headache or fatigue) on admission.
Time of onset of the symptoms should be acute ( Days ≤ 10).
SpO2 ≤ 88%
Respiratory Rate ≥ 24

Exclusion Criteria:

Refusal to participate expressed by patient or legally authorized representative if they are present.
Patients with prolonged QT or PR intervals, Second or Third Degree heart block, Arrhythmias including torsade de pointes
Patients using drugs with potential interaction with Umifenovir Hydroxychloroquine, 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.

Contacts and Locations

Information from the National Library of Medicine

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): NCT04350671

Locations

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Iran, Islamic Republic of
Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services
Tehran, Iran, Islamic Republic of

Sponsors and Collaborators

Shahid Beheshti University of Medical Sciences

Investigators

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Study Chair:	Ilad Alavi Darazam, MD	Shahid Beheshti University of Medical Sciences
Study Director:	Shervin Shokouhi, MD	Shahid Beheshti University of Medical Sciences
Principal Investigator:	Minoosh Shabani, MD	Shahid Beheshti University of Medical Sciences
Principal Investigator:	Mohammadreza Haji Esmaelie, MD	Shahid Beheshti University of Medical Sciences
Principal Investigator:	Seyed Sina Naghibi Irvani, MD, MPH, MBA	Shahid Beheshti University of Medical Sciences

More Information

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Responsible Party:	Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Dr., Shahid Beheshti University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT04350671
Other Study ID Numbers:	Interferon Beta 1a in COVID-19
First Posted:	April 17, 2020 Key Record Dates
Last Update Posted:	April 20, 2020
Last Verified:	April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
Plan Description:	There is no further information.

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Shahid Beheshti University of Medical Sciences:


COVID-19 Novel Coronavirus Interferon Beta 1a Lopinavir/Ritonavir Kaletra	Chloroquine Hydroxychloroquine Interferon SARS-CoV-2 2019-nCoV

Additional relevant MeSH terms:

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Interferons Ritonavir Lopinavir Interferon-beta Interferon beta-1a Hydroxychloroquine Antineoplastic Agents Antiviral Agents Anti-Infective Agents HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors	Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antimalarials Antiprotozoal Agents Antiparasitic Agents Antirheumatic Agents Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic

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