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  • Writer's pictureRichard Cree

Randomised, Embedded, Multi-factorial, Adaptive What Now!?

Updated: May 26, 2020

Saturday 23rd May 2020

Figures for 22nd May

UK COVID Deaths 351 / Total 36,393

James Cook Hospital – Total COVID deaths – 223

Nicky and I both have the day off today so I thought it would be an opportunity to post some information about the COVID-19 research that is going on within Critical Care at James Cook.

Research is being conducted by a dedicated team that includes Professor Bonner and Colonel Henning. Despite sounding like they have come straight from a game of Cluedo, they have managed to recruit every positive COVID-19 patient that has passed through the doors of Critical Care into a research trial.

This is no mean feat and would not have been possible without the work of Keith, the indomitable research nurse who appears to have managed to clone himself so that he can be anywhere and everywhere at the same time. It is his diligent work that is responsible for the fact that James Cook is currently the World’s top recruiting site for two Critical Care COVID-19 studies – the REMAP-CAP and GenOMICC trials.

Working with Keith is a lot like being Colonel Henry Blake to his Radar O’Reilly, for those of you that remember M*A*S*H. There isn’t a day that goes by that Keith doesn’t deploy his ninja skills to silently appear beside you with a sheath of research papers that need signing, before thrusting a pen into your hand.

Such research is vital in maximising our future patients’ chance of recovering from COVID-19. Given the limited treatment options currently available, time is of the essence.

COVID-19 infection can produce many different effects. There is a pneumonitis that affects the lungs, a ‘cytokine storm’ that causes multiple organ failure, thrombosis which causes blood clots in both arteries and veins, complex neurological effects and many other consequences that we are still discovering.

The Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia study is best shortened to REMAP-CAP unless you are the sort of tedious bore that can be found on some pub quiz teams. This research trail is an ‘advanced adaptive platform study’. This means that once the study has started, modifications can be made in order to make the trail more flexible, efficient and fast. It is investigating multiple drugs in the same study. These include antivirals such as a lopinavir-ritonavir combination. Also studied are anti-inflammatory drugs like the now-infamous hydroxychloroquine as well as tocilizumab, steroids and the anti-inflammatory effect of the antibiotic clarithromycin.

The big advantage of this type of study is that the results are continuously analysed whilst the study is being performed so that when any drug shows any positive result, then this can become a beneficial treatment immediately without awaiting the often protracted publication of results in the usual way.

One particularly important arm of the REMAP-CAP study is looking at the large increased risk of thrombosis and whether routinely anti-coagulating or thinning the blood of patients is beneficial or harmful. It will also be looking at using plasma from recovering COVID patients to treat new patients in the hope that the antibodies in donor plasma will be effective against the virus.

The adaptive nature of this study means that if one treatment is shown to work, it can be combined with another to see whether there is a cumulative benefit. For example, if an antiviral drug is shown to work, and an anti-inflammatory drug is shown to work then these will be combined together in the next phase of the trial to see if they work even better together.

Other treatments that are being explored include interleukin-7 which could stimulate the patient’s own lymphocytes to kill the virus and otilimab which may damp down the overactive immune response that is responsible for many of the adverse effects of a severe coronavirus infection.

The other trial, the Genetics of Susceptibility and Mortality in Critical Care (GenOMICC) study aims to investigate the effects of genetics on survival. It aims to identify the specific genes that cause some people to be more susceptible to particular infections and more likely to become critically ill. To do this, the study will compare cells from some COVID patients with those from healthy people. Identifying such genes may help to use existing treatments better or help design new treatments.

We are only conducting serious research at James Cook. I must reassure you that at no point do we plan to study the effects of intravenous disinfectant or ‘bringing tremendous light inside the body’ as a means of combating COVID-19.

And for all you Cluedo fans out there, I can confirm that it was Professor Bonner, in the Library, with the Candlestick. Keith quickly and efficiently disposed of the body. You know how cut-throat the world of academic research can be…

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Jul 29, 2020

i realise this is an old post (missed it first time round) - but someone living within half a mile of JCUH (regularly see the "chopper" land, im that close) - its exciting, if thats appropriate, to think that our lil slice of the UK is at the forefront. proud of that!


May 24, 2020

Fantastic that our local hospital is top, it will no doubt put our name on a very large map! Keep up the great work to everyone involved. I hope your blog continues well past COVID too 😷 its really interesting and informative.


May 24, 2020

Have to agree with alwaysdebi that there is so much conflicting information out there that I really enjoy reading your blogs. I worked for the trust from 1982 to retirement in 2018 and find it so reassuring that you are leading with so much research. Although I retired from the trust I am still working in the trust but employed by NHSP. Please keep up the good work and stay safe.


May 24, 2020

Really interesting read, so good to hear that James Cook is at the forefront with research. There’s so much out there on social media that you just don’t know what to believe. It’s very overwhelming but it makes me feel a whole lot better reading your blog from the front line which is factual and real. Thanks so much for taking the time to keep this blog going and for all you & your colleagues are doing 🌈💙👏🏻


May 23, 2020

You mean you’re not just injecting Cillit Bang ...Bang and the covid is gone?! 🧼💡

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