A randomized clinical trial, recently conducted by Dr. Rajan Ravichandran and colleagues on the safety and efficacy of NSAID Indometacin, revealed that it is not only safe but also very effective drug which can be used for the treatment of COVID-19 patients. Their study recently appeared in MedRxiv.
Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms.
Now, Dr. Rajan Ravichandran and colleagues conducted a randomized clinical trial at Panimalar Medical College, Chennai, India in order to test the efficacy and safety of Indometacin in RT-PCR positive covid patients.
“Our primary aim is to understand the efficacy of indomethacin in preventing desaturation and deterioration in mild and moderate Covid-19 patients and compare this with a paracetamol based arm. While, secondary aim is to evaluate symptomatic relief in indometacin patients compared to patients on paracetamol.”— they said.
They recruited a total of 300 patients using a block randomization parallel group protocol after obtaining the Ethics Committee clearance and consent from the patients. Finally, they presented results for 210 patients with 102 in the indomethacin arm and 108 in the paracetamol arm.
They found that, no patients developed hypoxia/desaturation in the indomethacin arm, while nearly 20 per cent of the patients in the paracetamol arm developed desaturation.
“When the SpO2 level dips below 93, the patient is managed with low-flow oxygen or by placing him/her in prone position to enhance breathing. In this study, no one showed further deterioration.”— they said.
The noticeable point is that in the indomethacin arm, the SpO2 improved just after one or two doses. Many patients in the marginal level of 94 improved.
At the end of the seventh day, a further 13 patients in the paracetamol arm were at a SpO2 level of 94. In the indomethacin arm, only two patients had a SpO2 levels of 94, while 97 of the 102 patients recorded an SpO2 level higher than 97.
Additionally, the symptomatic relief is even more salient. The median time for becoming afebrile in the indomethacin arm was three days compared to seven in the paracetamol arm. The median time for cough reduction was four days in the indomethacin arm compared to seven in the case of the paracetamol arm. In fact, 59 out of 108 patients in the paracetamol arm had fever on the seventh day but none in the indomethacin arm. Forty-nine out of 75 patients taking paracetamol took seven or more days to recover from cough. Only nine out of 70 patients took seven days and beyond in the indomethacin arm.
“The median time for becoming afebrile, cough reduction and myalgia relief in the indomethacin arm was four and three and four days respectively. On the other hand, in the paracetamol arm, the median time was seven and eight and seven days, respectively.”— they said.
One of the most important conclusion comes from analysing the IQR. One can notice in figs 2a to 2e, a very thin IQR band for fever and cough reduction along with a small error bar, compared to paracetamol. This clearly shows that indomethacin acts independent of the patient profile. A marginally broader IQR brand in myalgia may be because of the subjective nature of the relief.
They also monitored CRP, a marker of inflammation, on admission and discharge and found that, indomethacin is very effective in reducing CRP in patients with higher CRP in admission (more than 41 mg/L). R² value for indomethacin was much higher at 0.85, compared to 0.1. One may, hence, conclude that the consistency of indomethacin in reducing inflammation is very high.
A fourteen-day follow-up further reveals the efficacy of the drug. In the indomethacin arm nearly 50 per cent had fully recovered compared to 28 % in the paracetamol arm. The only complaint by patients who took indomethacin was tiredness. Many of these patients had gone back to normal work, too. While, the paracetamol arm patients had several discomfort including myalgia, joint pain and tiredness.
“The use of Indomethacin, alongside the standard treatment protocol in hospitalised Covid-19 patients, was associated with marked symptomatic relief and the oxygen saturation level being maintained at a high level. There were no adverse effects. Indomethacin, instead of paracetamol, should be a preferred drug for the treatment of mild and moderate Covid-19 patients.”— they concluded.
Reference: Rajan Ravichandran, Surapaneni Krishna Mohan, Suresh Kumar Sukumaran, Devakumar Kamaraj, Sumetha Suga Daivasuga, Samson Oliver Abraham Samuel Ravi, Sivakumar Vijayaraghavalu, Ramarathnam Krishna Kumar, “Use of Indomethacin for mild and moderate Covid -19 patients A Randomized Control Trial”, medRxiv 2021.07.24.21261007; doi: https://doi.org/10.1101/2021.07.24.21261007
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