BMJ win for a surprising trial
FEAST, a clinical trial that assessed how to treat children in Africa for shock, has won the BMJ paper of the year for 2012. Lead researcher Kath Maitland and research uptake coordinator Annabelle South discuss the surprising results of the research.
Many children admitted to hospital in Africa with infections are also found to be suffering from shock, a condition where blood is not being pumped around the body properly. This can be caused by diseases such as malaria and sepsis and up to a fifth of children with shock die within hours of arriving.
We designed FEAST, which stands for ‘Fluid Expansion As Supportive Therapy’,to test whether giving children fluid rapidly (boluses) via a drip could restore their normal circulation. This is done as standard in higher income countries but because it’s not generally used in Africa, it was important for us to test it in a controlled trial — where children were randomly assigned to receive boluses or to receive fluid slowly.
When the independent committee responsible for monitoring the safety and progress of the trial requested that we stop recruitment ahead of schedule, all the researchers and doctors involved assumed that it was because the treatment was working so well that the committee had already reached a conclusion on its benefits. They had seen children looking better immediately after receiving fluids, and not developing the potential side effects they had been warned to look out for.
But we were stunned when we found out that there was clear evidence that the treatment was actually harming children (compared to being given fluid slowly). Even children whose circulation had seemed to improve were at higher risk of dying than children who received fluid slowly.
Since the trial was stopped we have spent a lot of time trying to work out why this rapid delivery of fluid is harmful, and we are still not sure. What we do know is that the trial provides the strongest evidence so far on the (lack of) effectiveness of the treatment for children in shock caused by severe infections. Up until the FEAST results came out, the only other trials carried out had compared different types of fluid, but not whether or not giving fluid rapidly is beneficial in the first place.
We are very happy to win BMJ paper of the year. It’s always nice to have recognition of your achievements, and conducting FEAST took a lot of effort from many people in Africa and the UK. It demonstrates that high quality trials can be conducted in normal hospitals inAfrica. The results of the trial also show how important it is to carry out trials to test treatments in new settings.
We are now working on analysing the data for any clues as to why fluid resuscitation is harmful, and pushing for national and international guidelines to change in the light of our results. The scientific community should also do further work to understand whether the results of FEAST may be relevant in high-income countries too.
Kath Maitland, Professor of Tropical Paediatric Infectious Disease, Imperial College London
Annabelle South, Policy, Communications & Research Uptake Coordinator, MRC Clinical Trials Unit
The FEAST trial was funded by the MRC and DFID (through a concordat with MRC), sponsored by Imperial College London and coordinated by the KEMRI-Wellcome Trust Research Programme in Kenya in collaboration with scientists from Imperial College and the MRC Clinical Trials Unit.
The paper was published in the New England Journal of Medicine in June 2011.