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

Alavi Darazam, Ilad; Hatami, Firouze; Mahdi Rabiei, Mohammad; Amin Pourhoseingholi, Mohamad; Shabani, Minoosh; Shokouhi, Shervin; Mardani, Masoud; Moradi, Omid; Javandoust Gharehbagh, Farid; Mirtalaee, Nasrinsadat; Negahban, Halimeh; Amirdosara, Mahdi; Zangi, Masoud; Hajiesmaeili, Mohammadreza; Kazempour, Muhanna; Shafigh, Navid

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-β 1a compared to low dose IFN-β 1a in severe COVID-19 cases. METHODS: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-β 1a (Recigen) (Subcutaneous injections of 88 μg (24 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally) and the control group was treated with low-dose IFN-β 1a (Recigen) (Subcutaneous injections of 44 μg (12 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally). RESULT: A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-β1a was shorter than that for cases treated with high-dose IFN-β1a (6 vs 10 days; P = 0.018). The mortality rates in intervention and control group were 41% and 36.5%, respectively. CONCLUSION: The use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-β 1a. Trial registration: This trial has been registered as ClinicalTrials.gov, NCT04521400.