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Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial.
Trials. 2020 Nov 23; 21(1):939.T

Abstract

BACKGROUND

Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.

METHODS

This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.

DISCUSSION

Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.

TRIAL REGISTRATION

EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.

Authors+Show Affiliations

Unit of Internal Medicine, IRCCS Ospedale San Raffaele, Milan, Italy. bosi.emanuele@hsr.it. Vita-Salute San Raffaele University, Milan, Italy. bosi.emanuele@hsr.it.University of Milan Medical School, Milan, Italy.Unit of Internal Medicine, IRCCS Ospedale San Raffaele, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy. Unit of Virology, IRCCS Ospedale San Raffaele, Milan, Italy.Clinical Trial Center, IRCCS Ospedale San Raffaele, Milan, Italy.Clinical Trial Center, IRCCS Ospedale San Raffaele, Milan, Italy.Clinical Trial Center, IRCCS Ospedale San Raffaele, Milan, Italy.Clinical Trial Center, IRCCS Ospedale San Raffaele, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy. Unit of Virology, IRCCS Ospedale San Raffaele, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy. Unit of Radiology, IRCCS Ospedale San Raffaele, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy. Unit of Neurology, IRCCS Ospedale San Raffaele, Milan, Italy.Clinical Trial Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

33225960

Citation

Bosi, Emanuele, et al. "Interferon Β-1a (IFNβ-1a) in COVID-19 Patients (INTERCOP): Study Protocol for a Randomized Controlled Trial." Trials, vol. 21, no. 1, 2020, p. 939.
Bosi E, Bosi C, Rovere Querini P, et al. Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. Trials. 2020;21(1):939.
Bosi, E., Bosi, C., Rovere Querini, P., Mancini, N., Calori, G., Ruggeri, A., Canzonieri, C., Callegaro, L., Clementi, M., De Cobelli, F., Filippi, M., & Bregni, M. (2020). Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. Trials, 21(1), 939. https://doi.org/10.1186/s13063-020-04864-4
Bosi E, et al. Interferon Β-1a (IFNβ-1a) in COVID-19 Patients (INTERCOP): Study Protocol for a Randomized Controlled Trial. Trials. 2020 Nov 23;21(1):939. PubMed PMID: 33225960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. AU - Bosi,Emanuele, AU - Bosi,Carlo, AU - Rovere Querini,Patrizia, AU - Mancini,Nicasio, AU - Calori,Giliola, AU - Ruggeri,Annalisa, AU - Canzonieri,Cecilia, AU - Callegaro,Luciano, AU - Clementi,Massimo, AU - De Cobelli,Francesco, AU - Filippi,Massimo, AU - Bregni,Marco, Y1 - 2020/11/23/ PY - 2020/07/24/received PY - 2020/11/03/accepted PY - 2020/11/23/entrez PY - 2020/11/24/pubmed PY - 2020/11/27/medline KW - COVID-19 KW - IFNβ-1a KW - SARS-CoV-2 SP - 939 EP - 939 JF - Trials JO - Trials VL - 21 IS - 1 N2 - BACKGROUND: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination. METHODS: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients. DISCUSSION: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment. TRIAL REGISTRATION: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/33225960/Interferon_β_1a__IFNβ_1a__in_COVID_19_patients__INTERCOP_:_study_protocol_for_a_randomized_controlled_trial_ DB - PRIME DP - Unbound Medicine ER -