A randomized controlled trial of combined ivermectin and zinc sulfate versus combined hydroxychloroquine, darunavir/ritonavir, and zinc sulfate among adult patients with asymptomatic or mild coronavirus-19 infection
Prof. Yupin Yupin Suputtamongkol, Sireethorn Nimitvilai, Ussanee Poolvivatchaikarn, Dechatorn Rassamekulthana, Nuttawut Rongkiettechakorn, Anek Mungaomklang, Susan Assanasaen, Ekkarat Wongsawat, Chompunuch Boonarkart, Waritta Sawaengdee
Journal of Global Infectious Diseases, doi:10.4103/jgid.jgid_281_21
IntRoductIon The outbreak of coronavirus-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused an ongoing burden on health-care systems worldwide. Both the asymptomatic and symptomatic patients had similar viral loads. Published data showed that the transmission from asymptomatic or mild infection is very high. [1, 2] The administration of an effective oral antiviral therapy would be useful for transmission blocking or reducing onward transmission by these population. In addition, early treatment of these patients may prevent progression to severe COVID-19. However, an effective treatment option is not yet available for SARS-CoV-2 infection. Ivermectin is a safe and widely used antiparasitic drug with known in vitro efficacy against several single-strain RNA viruses, including SARS-CoV-2. [3] Ivermectin has been Introduction: Ivermectin, hydroxychloroquine (HQ), and darunavir/ritonavir are widely prescribed as an oral treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection despite their uncertainty of clinical benefit. The objective is to determine the safety and the efficacies of two treatment regimens against SARS-CoV-2 infection. Methods: We conducted an open-labeled, randomized, controlled trial to compare the efficacy between a 3-day course of once-daily high-dose oral ivermectin plus zinc sulfate (Group A) and a combination of HQ, darunavir/ritonavir, and zinc sulfate (HQ + antiretroviral, Group B) for 5 days in asymptomatic or mild SARS-CoV-2 infection. The study period was between December 2020 and April 2021. Results: Overall, 113 patients were randomized and analyzed (57 patients in Group A and 56 patients in Group B). The median duration to achieve the virological outcome of either undetected or cycle threshold (Ct) for N gene of SARS-CoV-2 by real-time polymerase chain reaction was 6 days (95% confidence interval [CI] 5.3-6.7) versus 7 days (95% CI: 5.4-8.6) in Group A and Group B, respectively (P = 0.419) in the modified intention-to-treat population. All patients were discharged from hospital quarantine as planned. Two patients in Group A and one patient in Group B were considered clinically worsening and received 10 days of favipiravir treatment. There was no serious adverse event found in both groups. Conclusion: We demonstrated that both treatment regimens were safe, but both treatment regimens had no virological or clinical benefit. Based on this result and current data, there is no supporting evidence for the clinical benefit of ivermectin for coronavirus-19.
Research quality and ethics statement The authors followed applicable EQUATOR Network (http:// www.equator-network.org/) guidelines during this research project. This study was approved by the appropriate Institutional Review Board of all study sites, the Council of Architecture (COA 323/2563), and (COA 002/2021). The trial was registered with ClinicalTrials.gov (NCT02045069).
Conflicts of interest There are no conflicts of interest.
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