Efficacy and Safety of Molnupiravir in Mild COVID-19 Patients in India

Abstract

BackgroundAt 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). MethodologyThis 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). ResultsEligible 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. ConclusionsThe 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.

Clinical efficacy and safety of molnupiravir for nonhospitalized and hospitalized patients with COVID‐19: A systematic review and meta‐analysis of randomized control trials

“…None of the studies were excluded on the basis of a quality assessment performed using the Cochrane risk-of-bias tool 2.0 (Figure 2). Four studies presented low risk of bias in all domains, 9,14,15,23 four studies presented a moderate risk of bias, [19][20][21][22] and one study presented a high risk of bias. 16 Among the domains that were evaluated in the nine studies, high risk of bias was detected with respect to the randomization process, deviations from the intended intervention, and missing outcome data.…”

“…9,12,13,15,16,[19][20][21][22] Four studies 12,13,15,19 were phase-2 RCTs and the other five were phase 3 studies. 9,16,[20][21][22] One study was a single-center study and the other eight were multicenter trials, 9,12,13,15,16,19-21 of which three were multinational studies. 9,12,19 Seven RCTs 9,12,13,15,16,20,21 focused on nonhospitalized patients and two 19,22 only included hospitalized patients.…”

“…9,16,[20][21][22] One study was a single-center study and the other eight were multicenter trials, 9,12,13,15,16,19-21 of which three were multinational studies. 9,12,19 Seven RCTs 9,12,13,15,16,20,21 focused on nonhospitalized patients and two 19,22 only included hospitalized patients. Five 9,12,13,15,19,22 and four 16,[20][21][22] RCTs used placebo and standard of care as comparators, respectively.…”

“…9,12,19 Seven RCTs 9,12,13,15,16,20,21 focused on nonhospitalized patients and two 19,22 only included hospitalized patients. Five 9,12,13,15,19,22 and four 16,[20][21][22] RCTs used placebo and standard of care as comparators, respectively. The present study included a total of 30 675 patients, of which 15 469 received molnupiravir as an intervention and 15 206 belonged to a control group (placebo or standard of care).…”

Impact of COVID-19 on Cardiovascular Disease

“…However, recent data suggest that treatment regimens with nirmatrelvir/ritonavir and remdesivir seem to be slightly more effective than molnupiravir [ 232 ], and therefore, the NIH recommends the use of molnupiravir only if nirmatrelvir/ritonavir and remdesivir are not available [ 194 ]. In general, the use of molnupiravir appears to be safe, and in terms of the effects on the CV system, there were no reports of cardiac side effects in randomized trials examining molnupiravir thus far [ 231 , 233 , 234 , 235 , 236 ].…”