Launched at the start of April, the Adaptive Covid-19 Treatment Trial (ACTT-EU/UK) trial, is taking place in about 75 hospitals globally, with the Medical Research Council (MRC) Clinical Trials Unit at UCL leading the UK and EU study. Other sites in the EU (Spain, Denmark and Germany) were coordinated by the University of Copenhagen.
The randomised controlled trial, which has recruited more than 1000 patients globally, aims to evaluate the safety and efficacy of the anti-viral drug remdesivir, as a treatment for Covid-19.The drug was originally developed to treat Ebola and Marburg virus infections. The UCL-led part of this trial has recruited 79 patients, including 46 from the UK, and 33 from Greece and was closed to new enrolments on April 19.
Preliminary results released yesterday (Wednesday 29 April 2020) by the US National Institute of Allergy and Infectious Diseases (NIAD) shows the speed of recovery for hospitalised Covid-19 patients treated with the drug was 31% faster than for those patients who had the placebo.
Specifically, the average time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Preliminary results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group.
Recovery in this study was defined in three ways: being well enough to come off oxygen although remaining in hospital; being well enough for hospital discharge although not quite back to normal health; or being out of hospital and returned to normal activity levels. In the trial, patients were given remdesivir every day for 10 days while they remained in hospital.
The analysis was put together by an independent Data and Safety Monitoring Board (DSMB), which is overseeing the trial.
Professor Mahesh Parmar, Director of the MRC Clinical Trials Unit at UCL, who has overseen the trial in the EU, said: “This is the first large scale international trial to report on the use of the drug remdisivir to treat patients hospitalised with Covid-19. These results are very promising indeed. They show that this drug can clearly improve time to recovery. Before this drug can be made more widely available, a number of things need to happen: the data and results need to be reviewed by the regulators to assess whether the drug can be licensed and then they need assessment by the relevant health authorities in various countries. While this is happening we will obtain more and longer term data from this trial, and other ones, on whether the drug also prevents deaths from Covid-19.”
Co-study lead, Professor Sarah Pett, Professor of Infectious Diseases at the MRC Clinical Trials Unit at UCL, said: “Delivering the results of the first stage of the ACTT study in such a short time is down to the dedication and hard work of the teams in the USA, at UCL, all of the hospitals who participated in this trial, and of course most importantly, the patients who agreed to participate. The spirit of collaboration has never been stronger, in this time of urgent global need. The reward for all of us has been to provide data which suggests remdesivir helped the patients in the ACTT study recover more quickly. This is a foundation on which to build, and these findings will help other patients with Covid-19.”
Co-study lead, Professor Abdel Babiker, Professor of Epidemiology and Medical Statistics at the MRC Clinical Trials Unit at UCL, said: “These are very encouraging results from the first large randomised international trial to report on the treatment of Covid-19. To speed up the identification of effective treatments the design of this trial is adaptive which facilitates the speedy identification of effective treatment by testing promising agents as they come along in different stages of the trial. These results are from the first stage and other stages are being planned. Conducting clinical trials during a pandemic is very challenging and the accomplishment of this stage in record time is testament to the strong international collaboration and the flexibility of the regulatory authorities and Ethics committees in adopting a fast-tracked but rigorous evaluation in their approval process.”
About the trial
Adults hospitalised with Covid-19 were allocated at random to receive either remdesivir or a placebo via a drip for up to ten days, while they are in hospital. The trial was double blinded, which means that neither the patients nor their doctors knew if they have received remdesivir or a placebo. This helps investigators tell whether any improvements are due to the study treatment or not. People taking part in the trial were followed up for 29 days. Initially the trial aimed to recruit 440 people but this number was increased to 800, with these numbers being exceeded by several hundred by April 19. Researchers hoped to have the first results from the trial by the beginning of this summer, but were actually able to find results several months ahead of schedule, due to fast recruitment of patients.
The ACTT-EU/UK trial has an adaptive design, an area which the MRC Clinical Trials Unit at UCL has been pioneering for many years, which means if new treatments are identified that might help patients with severe Covid-19, they can be immediately added to the trial. If this happens, the number of people needed in the trial will change.
The trial, which is funded by the National Institutes of Health (NIH) in the USA and supported by the NIHR, is also taking place in USA, Japan, South Korea, Denmark, Germany, Greece and there are plans to open it in Spain, Italy and other EU countries.