CaPPtain's Blog

  • CaPPtain's Blog: John Burn, December 2020

    posted on Monday, 4th January 2021

    Not tagged.

    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

  • CaPPtain's Blog: John Burn, June 2020

    posted on Tuesday, 16th June 2020

    Not tagged.

    Well, we finally got there.  The 10-year follow up paper on the CAPP2 study is now published in the Lancet (13th June 2020)*.  It may seem a long time since the 2011 CAPP2 paper but we wanted to extend the analysis to include the second decade for those who started earliest. Our aim was to see if the protective effect seen in our 2011 analysis persisted for more than the average of 5 years since starting in the trial.

    The important take home message is that the effect was even clearer than in 2011, the protective effect of aspirin against colorectal cancer has persisted in this long-term follow up, for up to 20 years.  The gold standard test in any randomised trial is to demonstrate a significant difference on "Intention to Treat".  This means that everyone who started in the aspirin part of the trial is included, whether or not they stuck with the treatment.  This is a very hard test and the result did not reach the necessary levels of statistical significance last time in 2011, but this time it did, providing convincing evidence that the effect is due to an overall cancer preventative property of aspirin.

    When asking how big the difference was, known as "efficacy", it still is sensible to look at all the cancers in the LS folk who took the treatment for the planned two years at least.  We judged this as people who had taken a total of 1400 trial tablets over that time period.  The statistical analysis of this group showed there were half as many colon cancers in those who took aspirin regularly during the trial.  Obviously, many may have taken aspirin in the subsequent years after completing the CAPP2 trial but this might apply to all the participants.  The only difference between the two groups was the couple of years on the trial when one group had real aspirin tablets and the other had placebo tablets.

    For those of you who like the real numbers, here they are:  427 people took aspirin and 40 of them got colon cancer.  Two of them got colon cancer twice, so there were 42 bowel cancers over an average of 10 years follow up.  434 people were in the placebo group and 58 of them got colon cancer, some more than once making a total of 71 bowel cancers, that's 29 more than the aspirin group.  

    The UK National Institute for Healthcare and Clinical Excellence (NICE) announced in January 2020, based on the evidence from the 2011 CAPP2 paper, that aspirin should be recommended to all adults with Lynch syndrome.  NICE noted that the CaPP3 study would provide information on the optimal dose but in the meantime supported a lower dose.  We are recommending 150mg daily for people of average size, less if you are of small build and more if you are heavier.  This is based on the recent work of Peter Rothwell reanalysing the old trial data and, on our paper, looking at the higher cancer risk in LS people who were overweight.   The Australian authorities have now endorsed use of aspirin in LS and our European survey organised by the European Hereditary Tumour Group has just been accepted for publication and shows general professional support.  It is still a recommendation and we need to get cancer prevention listed for aspirin in the British National Formulary.

    The other big news is, of course, theCovid-19 pandemic.  We are aware that some participants in CaPP3 stopped their aspirin after newspaper reports that non-steroidal anti-inflammatory drugs might make the illness worse.  We now know this is not true.  In fact, a couple of Covid-19 trials have now started including aspirin as a treatment because it has been shown that excessive clotting is part of the illness.  We are planning an aspirin trial in early Covid-19 cases in Newcastle too.  The take home message is thatIT'S OK TO TAKE ASPIRIN!  People in CaPP3 can return to their prescribed aspirin.  As follow up appointments are arranged, we will need to know who stopped taking their aspirin and for how long, so we can include this in the final CaPP3 analysis in 2024.

    If you have Lynch syndrome and are not on the trial, then this blog and the CAPP2 Lancet paper will support discussions with your doctor to discuss regularly taking aspirin.  Make sure your blood pressure is normal and that you don't have a treatable Helicobacter pylori infection in your stomach, as many people still do.  If clear, then take some aspirin to reduce your colon cancer risk.

    Thanks again to all the people who are taking part in CaPP3. And a special thank you to the CaPP3 participants who have completed the five years of study aspirin. You will be receiving a personal thank you letter from the study (once approved by the ethics committee). The CaPP3 study will keep in contact with you annually after your Year 5 contact. As we have shown in CAPP2, your participation in these trials is essential if we are to change clinical practice. We still need to know the best dose, so if you are in CaPP3, please keep taking the study aspirin.

    John Burn
    16th June 2020

    *Additional links

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