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

• ClinicalTrials.gov Identifier: NCT04521400
• Recruitment Status: Unknown
• First Posted: August 20, 2020
• Last Update Posted: August 20, 2020
• Sponsor: Shahid Beheshti University of Medical Sciences
• Information provided by (Responsible Party): Ilad Alavi Darazam, Shahid Beheshti University of Medical Sciences

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: High dose Interferon-beta 1a; Drug: Lopinavir/Ritonavir; Drug: Low dose Interferon-beta 1a	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: August 20, 2020
• Estimated Primary Completion Date: September 4, 2020
• Estimated Study Completion Date: September 11, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Ilad Alavi Darazam, MD; +98-914-149-1958; ilad13@yahoo.com

Sponsors and Collaborators

Shahid Beheshti University of Medical Sciences

Investigators

• Study Chair: Ilad Alavi Darazam, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Firouze Hatami, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Mohammad Mahdi Rabiei, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Omid Moradi; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Behnam Rahimi, M.D; Shahid Beheshti University of Medical Sciences
• Study Director: Shervin Shokouhi, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Mohammad Reza Hajesmaeili, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Minoosh Shabani, M.D; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Seyed Sina Naghibi Irvani, M.D; Shahid Beheshti University of Medical Sciences

More Information

Publications:

Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 27;367(6485):1444-1448. doi: 10.1126/science.abb2762. Epub 2020 Mar 4.

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020 Mar 27;11(1):1620. doi: 10.1038/s41467-020-15562-9. Erratum in: Nat Commun. 2021 Apr 1;12(1):2144.

Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):541-543. doi: 10.1038/s41423-020-0401-3. Epub 2020 Mar 17.

Wang BX, Fish EN. Global virus outbreaks: Interferons as 1st responders. Semin Immunol. 2019 Jun;43:101300. doi: 10.1016/j.smim.2019.101300. Review.

Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, Ng YY, Lo J, Chan J, Tam AR, Shum HP, Chan V, Wu AK, Sin KM, Leung WS, Law WL, Lung DC, Sin S, Yeung P, Yip CC, Zhang RR, Fung AY, Yan EY, Leung KH, Ip JD, Chu AW, Chan WM, Ng AC, Lee R, Fung K, Yeung A, Wu TC, Chan JW, Yan WW, Chan WM, Chan JF, Lie AK, Tsang OT, Cheng VC, Que TL, Lau CS, Chan KH, To KK, Yuen KY. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10.

Hensley LE, Fritz LE, Jahrling PB, Karp CL, Huggins JW, Geisbert TW. Interferon-beta 1a and SARS coronavirus replication. Emerg Infect Dis. 2004 Feb;10(2):317-9.

Dastan F, Nadji SA, Saffaei A, Marjani M, Moniri A, Jamaati H, Hashemian SM, Baghaei P, Abedini A, Varahram M, Yousefian S, Tabarsi P. Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial. Int Immunopharmacol. 2020 Aug;85:106688. doi: 10.1016/j.intimp.2020.106688. Epub 2020 Jun 7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Alavi Darazam I, Hatami F, Mahdi Rabiei M, Amin Pourhoseingholi M, Shabani M, Shokouhi S, Mardani M, Moradi O, Javandoust Gharehbagh F, Mirtalaee N, Negahban H, Amirdosara M, Zangi M, Hajiesmaeili M, Kazempour M, Shafigh N. An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a in severe COVID-19: The COVIFERON II randomized controlled trial. Int Immunopharmacol. 2021 Oct;99:107916. doi: 10.1016/j.intimp.2021.107916. Epub 2021 Jun 29.

Alavi Darazam I, Hatami F, Rabiei MM, Pourhoseingholi MA, Moradi O, Shokouhi S, Hajesmaeili MR, Shabani M, Irvani SSN. An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19: A structured summary of a study protocol for a randomized controlled l trial. Trials. 2020 Oct 26;21(1):880. doi: 10.1186/s13063-020-04812-2.

• Responsible Party: Ilad Alavi Darazam, Dr. Ilad Alavi Darazam, MD, Shahid Beheshti University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT04521400
• Other Study ID Numbers: Interferon in COVID
• First Posted: August 20, 2020
• Last Update Posted: August 20, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by Ilad Alavi Darazam, Shahid Beheshti University of Medical Sciences:

COVID-19; Interferons; Ritonavir; Lopinavir; Interferon-beta; Antiviral Agents; Anti-Infective Agents; Immunologic Factors

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Interferons; Ritonavir; Lopinavir; Interferon-beta; Interferon beta-1a; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; HIV Protease Inhibitors; Viral 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; Immunologic Factors