From proposed treatment to world's leading medical journals
St John of God Health Care Director of Research, Professor Steve Webb was a senior author of two clinical trials published this month in the New England Journal of Medicine (NEJM) and American Journal of Medicine (JAMA).
2 Nov 2023
As one of the leaders of the world’s largest adaptive platform (perpetual) trial of treatment options for patients with severe COVID-19, Professor Webb, together with a team based at Monash University in Melbourne, released results about two of its treatments, vitamin C and simvastatin. Professor Webb reflects on the significance of the trials for the general population and for himself, as an intensive care specialist and researcher.
Some background on the team behind the trials
REMAP-CAP is an international consortium of Intensive Care Unit (ICU) specialists, infectious diseases physicians, and statisticians. We came together after the 2009 swine flu pandemic with the goal of being better prepared for the next pandemic. At the beginning of 2020, as COVID-19 was spreading we expanded REMAP-CAP so that it recruited more than 10,000 patients with COVID-19, enrolling patients at more than 300 hospitals in 30 countries.
REMAP-CAP is a special type of trial, known as an adaptive platform trial, that can start (and stop) testing new treatments on a continuous basis.
The results from REMAP-CAP have saved countless lives during the pandemic. Earlier results from the trial were available during the pandemic, were incorporated into international guidelines for how to treat COVID, and applied to patients globally.
Two of the results that I am most proud of are:
- We found that tociluzamab (a drug used to treat rheumatoid arthritis) was an effective treatment, saving one life for every 12 patients who received this treatment in an ICU.
- We also found that preventive treatment with therapeutic anticoagulation (anti-blood clotting medication) was harmful, leading to increased deaths. This was important because this treatment approach had become widely used and was withdrawn from practice following the results from REMAP-CAP.
Two findings, published this month by NEJM and JAMA
1. Simvastatin, a widely available and inexpensive drug that is included on the World Health Organisation list of essential medicines, was shown to have a high probability (96 per cent) of improving outcomes (a combination of survival and length of time patients need support in an intensive care unit) when started as a treatment for critically ill patients with COVID-19, and a 91 per cent chance of improving survival at three months. This equates to one life saved for every 33 patients treated with simvastatin. 2684 critically ill patients were included at 141 hospitals across 13 countries.
2. Vitamin C is widely available around the world and was used in some settings for the treatment of COVID-19. By combining two clinical trials – REMAP-CAP and LOVIT-COVID – over 2500 patients in 20 countries took part, including both critically ill and non-critically ill patients with COVID-19 in hospital. It was shown that high dose vitamin C did not improve outcomes for patients. This is the largest trial examining high-dose vitamin C in COVID-19 and provides evidence that high-dose vitamin C is not beneficial and suggests a high probability that it may be harmful.
What the findings mean for patients
Fortunately, because of vaccination, there is a much smaller proportion of patients with COVID-19 requiring treatment in an ICU. For patients who do require care in ICU, our results will continue to guide clinical treatment decisions.
The result for simvastatin is interesting because it turns out that a relatively inexpensive and widely used drug that many people take to lower their cholesterol was very likely an effective treatment for life-threatening COVID-19.
The result for vitamin C is also notable because it was widely promoted as an effective treatment. Our results show it was definitely not effective and was probably harmful. It just goes to show how important it is to actually test new treatment options in trials, rather than believe what the internet says is true!
Next up for REMAP-CAP
Our main focus now is investigating better treatments for life-threatening pneumonia and influenza. We are also ready for the next pandemic – just hoping that’s a long way away!
