In July 2021, noted nephrologist Rajan Ravichandran and Indian Institute of Technology (IIT), Madras professor R Krishna Kumar published the result of a randomised control trial (RCT) advancing the case use of indomethacin, a non-steroidal anti-inflammatory drug, to treat mild and moderate Covid-19 patients.
Since then, the case for indomethacin has been getting stronger with several international studies highlighting the benefits of the drug in the early stages of Covid treatment.
With a rapid rise in fresh coronavirus cases with mild and moderate symptoms, Professor Kumar explains why it is pertinent to include indomethacin in the Covid treatment protocol.Excerpts:
You have done two trials with indomethacin so far. What has been the outcome?
In early 2020, Dr Rajan suggested indomethacin to treat mild and moderate Covid-19 cases and designed a treatment protocol. Accordingly, we did the first trail matching 144 Covid positive patients in two arms (72 patients in indomethacin arm and 72 in paracetamol arm) using a statistical analysis called propensity score matching, which is accepted to mimic randomised control trial. We published the results in medRxiv in December 2020 and the peer-reviewed article was published in July 2021.
Then we did a randomised control trial (RCT) with 210 Covid-19 patients in two arms (103 patients in the indomethacin arm and 107 in paracetamol arm). In both studies, the age of the patients was from 18 to 80 and many had comorbidities.
What was the outcome of RCT?
We monitored fever, SpO2 (oxygen saturation), cough, body ache, and cold every day. After five days of treatment, 20 of the 107 patients in the paracetamol arm developed oxygen desaturation while none of the patients in the indomethacin arm developed desaturation.
Fever, cough and cold in the indomethacin group was resolved in half the time (3-4 days) as compared to paracetamol arm. We also did a 14-day follow up and found that most patients in the indomethacin arm had only tiredness while patients in the paracetamol arm had body and joint pain, stomach pain and tiredness. We published these results in medRxiv in July 2021.
Has the drug been included in the Covid-19 treatment protocol by the ICMR?
We made a presentation to the ICMR team in the presence of its chief Balram Bhargava sometime around July 2021. We have also sent the entire study, data and all supporting information to ICMR but yet to get any response.
Why has it not been approved so far?What could be the reason for the delay?
We do not know the reason. Some people say the sample size of the trial is small but I want to put out that these are statistical calculations based on the efficacy difference and the sample size cannot be commented upon without understanding the statistics. As long as it satisfies the statistics and gives a good measure of the efficacy, the size doesn’t matter.
Secondly, many people say it is not peer-reviewed. I would like to say that it is under peer review and typically the process takes a long time. That is why we have put all our 210 patient data in the public domain so that anyone from the healthcare community can review the data.
Could the delay be due to safety concerns of the drug?
It’s an old drug and has been in use since the 1960s. Over two million prescriptions of indomethacin are written every year in the US, so the safety of the drug is well established.
Are there any global studies supporting the use case of this drug?
The first study came from the University of California, San Francisco. They collected data on 244 Covid outpatients on indomethacin. Out of them, only one was required to go to hospital. It shows the need for hospitalisation for those treated with indomethacin is negligent.
A recent study in Italy also cited our research and followed our lead in using indomethacin instead of paracetamol. We were the first to do a proper trial and publish.
What do you expect from the government / policy makers?
We expect that indomethacin to be included in the protocol for Covid treatment because it’s a drug whose safety and efficacy are well established. It can either be a replacement to paracetamol or ICMR can say indomethacin can be used ‘at the discretion of the treating physician’. The drug acts on the virus post entry, and hence, acts independent of the variant.
Most importantly, the cost of treatment with indomethacin will be less than ₹100; so it’s both cheap and effective in Covid–19 treatment.