CaPPtain's Blog: John Burn, December 2020

As a challenging year draws to a close, I'm pleased to report that CaPP3 has been able to continue operating almost as normal. Some clinic appointments have been delayed but we have been able to maintain the core operation and issue prescriptions across the system.

In May 2021 we will reach a major trial milestone as the last recruits reach the end of the two years on blinded treatment. From then on, all people still in the trial will know what aspirin dose they have been allocated. You will remember the main purpose of this trial is to see if lower doses of aspirin are as protective as the 600mg dose we proved was effective in CAPP2. This is important because the side effects of aspirin increase with bigger doses. The two years of blinded treatment at the start are designed to collect reliable information about side effects on the three doses (600, 300 & 100mg aspirin), without any bias.

The main endpoint is counting how many colon and other cancers develop over the five years and beyond. In the meantime, the National Institute of Clinical and Care Excellence -  NICE NG151, has now recommended that everyone diagnosed with Lynch syndrome is advised by their doctors that aspirin is recommended to reduce the risk of cancer. This guidance has also gone out from NHS England to the Cancer Alliances across the country. The NICE guidance recognises that we don't know the best dose yet and that our CaPP3 trial will provide that answer. I am now recommending that people under 70kg take 150mg a day (a half standard tablet or two cardio aspirins) and people over that weight take 300mg or one standard aspirin a day until our intrepid CaPP3 community provide the answer in 2024.

Meanwhile, as we prepare for another Covid-19 shadowed year, I am pleased to say that there is now evidence that aspirin protects people from some of the worst effects of the virus. This is probably a combination of its anti-inflammatory effect and prevention of blood clotting. One of the surprising discoveries earlier this year was that Covid-19 patients have "sticky" blood which was blocking small blood vessels. You may recall that there were claims in the Spring that aspirin like drugs may cause a problem with Covid-19. I am now even more sure that it was "fake news" and people on CaPP3 can be reassured that staying in the trial is not a cause for concern.

The UK led RECOVERY trial now has an aspirin arm, investigating aspirin as a possible treatment for Covid-19. Also a scientific report* from Baltimore looked at whether people were taking aspirin when they were admitted to hospital with Covid-19, and compared their outcomes to those who were not. The people on aspirin did better. This is not as good as a proper randomised trial but it's encouraging. I've added the details of the paper by Jonathan Chow and colleagues at the end if you would like to read the paper.

I updated the virtual UK Cancer Genetics Group meeting last week about CaPP3, where I was able to thank colleagues across the UK and beyond for their continued support. May I take this opportunity to thank again all the people who have been in or are still taking part in the CaPP3 trial as well as all the study teams in the UK and internationally. Without your help we could never solve the problem of choosing the best dose of aspirin to prevent cancer in Lynch syndrome.

Enjoy the festive season as best you can, keep safe and all best wishes for 2021!

John Burn

18th December 2020

*Anesthesia & Analgesia Journal      Jonathan H. Chow et al 2020
Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In- Hospital Mortality in Hospitalized Patients with COVID-19 DOI: 10.1213/ANE.0000000000005292