An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

Abstract

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been presented as a broad-spectrum antiviral agent. This randomised clinical trial in a hospital setting evaluated the efficacy and safety of this drug in RT-PCR-positive coronavirus disease 2019 (COVID-19) patients. A total of 210 RT-PCR-positive COVID-19 patients who provided consent were allotted to the control or case arm, based on block randomisation. The control arm received standard of care comprising paracetamol, ivermectin, and other adjuvant therapies. The patients in the case arm received indomethacin instead of paracetamol, with other medications retained. The primary endpoint was the development of hypoxia/desaturation with SpO2 ≤ 93, while time to become afebrile and time for cough and myalgia resolution were the secondary endpoints. The results of 210 patients were available, with 103 and 107 patients in the indomethacin and paracetamol arms, respectively. We monitored patient profiles along with everyday clinical parameters. In addition, blood chemistry at the time of admission and discharge was assessed. As no one in either of the arms required high-flow oxygen, desaturation with a SpO2 level of 93 and below was the vital goal. In the indomethacin group, none of the 103 patients developed desaturation. On the other hand, 20 of the 107 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief than those in the paracetamol arm, with most symptoms disappearing in half the time. In addition, 56 out of 107 in the paracetamol arm had fever on the seventh day, while no patient in the indomethacin group had fever. Neither arm reported any adverse event. The fourteenth-day follow-up revealed that the paracetamol arm patients had faced several discomforts; indomethacin arm patients mostly complained only of tiredness. Indomethacin is a safe and effective drug for treating patients with mild and moderate covid-19.

Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents

“…An open-label randomised clinical trial in India evaluated the efficacy and safety of indometacin for patients hospitalised with COVID-19 with mild to moderate symptoms including fever, cough, and myalgia at admission. 90 None of the 103 patients randomly assigned to indometacin developed desaturation (SpO 2 ≤93%); however, desaturation did occur in 20 of the 107 patients allocated to paracetamol. Patients who received indometacin also had more rapid symptom relief than those given paracetamol, with most symptoms disappearing in half the time.…”

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID‐19: Might it also depend on their direct and/or indirect zinc chelating ability?

“…In line with this hypothesis, another paper showed that celecoxib could both prevent disease progression and promote recovery from COVID-19, whereas ibuprofen was less effective (Hong et al, 2020). Protective effects against COVID-19 were also shown for indomethacin or aspirin (Fazio et al, 2021;Perico et al, 2022;Ravichandran et al, 2022).…”

A 98-Year-Old Male With Paroxysmal Atrial Fibrillation Treated for COVID-19 at Home

“…Based on these pathophysiological mechanisms of the disease, various multidrug approaches were proposed for early outpatient treatment of mild COVID-19 [ 3 , 4 , 6 , 7 ]. Nonsteroidal anti-inflammatory drugs (NSAIDs) administered at the beginning of the symptoms have shown to significantly reduce hospitalization and disease duration in observational studies [ 3 - 5 , 9 ] and in a small open-label RCT [ 10 ]. While waiting for more solid evidence and generally approved guidelines, many GPs decided to treat outpatients at the first stage of the disease with commonly available over-the-counter drugs that had been previously suggested to prevent the progression of the disease.…”