Efficacy of the use of mefenamic acid combined with standard medical care vs. standard medical care alone for the treatment of COVID‑19: A randomized double‑blind placebo‑controlled trial

Abstract

Mefenamic acid is a non-steroidal anti-inflammatory drug exhibiting a wide range of anti-inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID-19; nasal/oropharyngeal swabs reverse transcription-PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two-arm, parallel-group, randomized, double-blind placebo-controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14-day follow-up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID-19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P= 0.020, Kaplan-Meier analyses using log-rank tests). Patients that received mefenamic acid plus standard medical care had a ~16-fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI,; P= 0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P= 0.008), retro-orbital eye pain (P= 0.049), and sore throat (P= 0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID-19. Due to its probable antiviral effects and potent anti-inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of cOVId-19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID‐19 patients

“…Having shown the infection of the microbiome and the replication of SARS‐CoV‐2 within it, we cannot dismiss the hypothesis of potential favourable and antiviral effects of certain NSAIDs, such as indomethacin or mefenamic acid, directly on the microbiome. Furthermore, further studies should be conducted to explore this hypothesis in depth, based on the observations made by 99,100 …”

“…Although in the present our study, the use of NSAIDs appears to not have a clinical impact it should not be excluded that other works show differently. Delgado‐Enciso et al, emphasize the importance of NSAIDs in a randomized double‐blind placebo‐controlled trial, phase II, on 36 subjects (19 study group and 17 control group) 100 . In this trial, the authors evaluated, during August‐December 2020 in Mexico, NSAIDs, mefenamic acid combined with standard medical care versus standard medical care alone, observing the time to initial clinical and symptomatic improvement of COVID‐19 patients, with an average of 4.4 days, for the study group, and 8 days for the control group.…”

Early Outpatient Treatment of COVID-19: A Retrospective Analysis of 392 Cases in Italy

“…This is the first study to describe attitudes and behaviours of physicians taking care of COVID-19 outpatients, and the outcomes and safety of early treatment of COVID-19 outpatients in the real world. The outpatient treatment of COVID-19 is still a relatively poorly investigated area, and the few existing studies consist of trials of either individual therapeutics [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] or fixed associations [ 30 ]. The studies so far performed in Italy include: a retrospective assessment of a combination of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed, on the risk of hospitalization in 158 patients with early COVID-19 [ 31 ]; and a retrospective matched-cohort study comparing 90 patients with mild COVID-19 who were treated at home according to a recommendation algorithm, with 90 matched patients who were treated with the same drugs without considering the algorithm [ 32 ].…”

Early Outpatient Treatment of Covid-19: A Retrospective Analysis of 392 Cases in Italy

“…This is the first study describing attitudes and behaviors of physicians taking care of COVID-19 outpatients, and the effectiveness and safety of early treatment of COVID-19 outpatient in the real world. Outpatient treatment of COVID-19 is still a relatively underinvestigated area and the few existing studies consist of trials of either individual therapeutics, for example hydroxychloroquine (Schwartz et al, 2021; Reis et al, 2021), colchicine (Tardif et al, 2021), azithromycin (Oldenburg et al, 2021; Hinks et al, 2021), NSAID (Guzman-Esquivel et al, 2022), corticosteroids (Clemency et al, 2022; Ezer et al, 2021; Ramakrishnan et al, 2021), antivirals (Roozbeh et al, 2021; Reis et al, 2021), antithrombotics (Connors et al, 2021), convalescent plasma (Korley et al, 2021), SARS-CoV-2 neutralizing antibodies (Gupta et al, 2021), interferons (Feld et al, 2021), sulodexide (Gonzalez-Ochoa et al, 2021), dietary supplements (Thomas et al, 2021), or fixed associations, for example hydroxychloroquine plus azithromycin (Rodrigues et al, 2021). In particular, studies so far performed in Italy include the retrospective assessment of a combination of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed, on the risk of hospitalization in 158 patients with early COVID-19 (Fazio et al, 2021), and a retrospective matched-cohort study comparing 90 patients with mild COVID-19 treated at home according to a recommendation algorithm (including NSAID, corticosteroids, anticoagulants, oxygen therapy and antibiotics) with 90 matched patients treated with the same drugs however without considering the algorithm (Suter et al, 2021).…”