Sinha Shubhadeep, N Kumarasamy, Suram Vasanth Kumar, Chary Sreenivasa S, Naik Sunil, Singh Veer Bahadur, Jain Manish K, Suthar Chandra P, Borthakur Swapnav, Sawardekar Vinayak, Sk Noushadali, Reddy Naveen, Talluri Leela, Thakur Pankaj, Reddy Mohan, Panapakam Muralidhar, Vattipalli Ramya
Clinical Development and Medical Affairs, Hetero, Hyderabad, IND.
Infectious Diseases Medical Centre, Voluntary Health Services, Chennai, IND.
Cureus. 2022 Nov 14;14(11):e31508. doi: 10.7759/cureus.31508. eCollection 2022 Nov.
Background At the peak of the coronavirus disease 2019 (COVID-19) pandemic, the need for an orally administered agent to prevent the progression of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became increasingly evident, which was the impetus behind our investigations with molnupiravir. Molnupiravir has been shown to be effective in preventing hospitalizations and/or clinical complications in patients with mild-to-moderate COVID-19. In this study, we evaluate the efficacy and safety of molnupiravir in Indian patients with mild SARS-CoV-2 infection and at least one risk factor for disease progression (CTRI/2021/05/033739). Methodology This was a phase III, multicenter, randomized, open-label, controlled study conducted in Indian adults aged 18-60 years with mild SARS-CoV-2, reverse transcription polymerase chain reaction (RT-PCR)-positive within 48 hours of enrollment in the study, and within five days of first symptom onset. Enrolled patients were randomized to treatment arms in a 1:1 ratio to receive molnupiravir or placebo in addition to the standard of care (SoC) for SARS-CoV-2 infection. The SoC was in compliance with Government of India guidelines that were in force at the time. The primary endpoint was the rate of hospitalization up to day 14. Safety endpoints included incidence of adverse events (AEs). Results Eligible patients were randomized in a 1:1 ratio to receive molnupiravir in addition to SoC treatment (n = 608) or SoC alone (n = 610). In the molnupiravir group, nine (1.48%) patients required hospitalization versus 26 (4.26%) patients in the control group (risk difference = -2.78%; 95% CI = -4.65, -0.90; p = 0.0053). Overall, 45 (3.70%) patients reported 47 AEs during the study, most of which were mild and resolved completely. The molnupiravir group reported 30 AEs compared to 17 AEs in the control group. Headache and nausea were the two most commonly reported AEs. Conclusions The molnupiravir arm showed a lower rate of hospitalization and a shorter time for the improvement of clinical symptoms coupled with early RT-PCR negativity. Molnupiravir was well tolerated, and AEs were mild and rare. The addition of molnupiravir to standard therapy has the potential to prevent the progression of mild COVID-19 disease to the severe form.
背景 在2019冠状病毒病（COVID-19）大流行高峰期，对一种口服药物以预防严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染进展的需求日益明显，这是我们对莫努匹拉韦进行研究的背后动力。莫努匹拉韦已被证明在预防轻至中度COVID-19患者住院和/或临床并发症方面有效。在本研究中，我们评估了莫努匹拉韦在患有轻度SARS-CoV-2感染且至少有一个疾病进展风险因素的印度患者中的疗效和安全性（CTRI/2021/05/033739）。
方法 这是一项III期、多中心、随机、开放标签、对照研究，针对年龄在18至60岁的印度成年人，他们患有轻度SARS-CoV-2感染，在研究入组后48小时内逆转录聚合酶链反应（RT-PCR）呈阳性，且在首次症状出现后五天内。入组患者以1:1的比例随机分配至治疗组，除接受SARS-CoV-2感染的标准治疗（SoC）外，分别接受莫努匹拉韦或安慰剂。SoC符合当时印度政府生效的指南。主要终点是至第14天的住院率。安全性终点包括不良事件（AE）的发生率。
结果 符合条件的患者以1:1的比例随机分配，除接受SoC治疗外，一组接受莫努匹拉韦治疗（n = 608），另一组仅接受SoC治疗（n = 610）。在莫努匹拉韦组中，9名（1.48%）患者需要住院治疗，而对照组为26名（4.26%）患者（风险差异 = -2.78%；95% CI = -4.65，-0.90；p = 0.0053）。总体而言，45名（3.70%）患者在研究期间报告了47起AE，其中大多数为轻度且完全缓解。莫努匹拉韦组报告了30起AE，而对照组报告了17起AE。头痛和恶心是最常报告的两种AE。
结论 莫努匹拉韦组的住院率较低，临床症状改善时间较短，同时RT-PCR早期转阴。莫努匹拉韦耐受性良好，AE轻微且罕见。在标准治疗中添加莫努匹拉韦有可能预防轻度COVID-19疾病进展为重症。
