Title: Building an international precision medicine platform trial for the acute respiratory distress syndrome (ARDS)
Funder: Medical Research Council

Abstract: Many patients admitted to Intensive Care Units require a machine, called a ventilator, to help them breathe. About 1 in 4 of these patients have a life-threatening condition with severe breathing difficulties called acute respiratory distress syndrome (ARDS). Unfortunately, around 1 in 3 of these patients with ARDS die from this condition in hospital. Over the last 30-years, various drug treatments have been tested to treat ARDS, with limited success. This project plans to develop a new approach to treating ARDS. The aim is to develop a trial which treats subgroups of patients with ARDS to find effective treatments. We want to test treatments in these subgroups of patients in a “platform” trial. Platform trials test multiple treatments at the same time. New treatments can be added to the trial in a structured way. This means that treatments can be assessed faster than setting up multiple trials. We also want to recruit patients across the world to this trial. This will speed up the time it takes to find out if a treatment works or not. Setting up such a trial is difficult. We need to do some work to be ready to start the trial. We will work with a broad range of experts alongside patients, carers, and family to develop the trial. We will decide how best to find patient subgroups. We will also work out the best treatments to study. We will work with the groups which fund and regulate clinical trials to make sure we deliver the best trial. We will work out the best way to collect and store patient’s samples. These samples will be used to understand how treatments work. No patients will be recruited at this stage of the trial development. Patients, carers and family are a central part of our team and so far, have helped us establish the need for this research and to write this proposal. They will continue to be involved at every stage of this project as well as the future trial. With the support of our PPI partners, we will share the information from this work in several ways including newspapers and social media. We will also publish the results in medical journals. This information from this project will help us set up the best trial to find new treatments for patients with ARDS. We hope that we can help create a new approach to testing new treatment for ARDS that can be used worldwide.

Lay abstract: The acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome characterised by acute hypoxaemic respiratory failure. The “syndromic” definition of ARDS ignores the significant clinical and biological heterogeneity within ARDS. A novel precision medicine approach to identifying pharmacological treatments for ARDS, targeting ARDS phenotypes which are linked to the host biological response, is urgently required. The objective of this application is to support the development of an international precision medicine platform trial aiming to efficiently test several pharmacological interventions in biological phenotypes in ARDS. This will be achieved by undertaking a series of interlinked work packages which will aim to: 1) define the best approach to phenotyping patients and prioritising initial interventions to be tested. 2) develop the study design and draft platform trial core (master) protocol and analysis plan. 3) undertake collaborative work with international regulators, sponsors and funders to define their individual requirements in the delivery of a UK led platform trial. 4) incorporate learning from existing platform trials. 5) build research capacity for clinical trial delivery. 6) engage with industry to develop pathways for testing novel agents and for sustainable funding. 7) develop a framework to embed biobanking globally within the platform trial. 8) ensure the patient and public voice is incorporated in every aspect of the trial design and execution. This project will be delivered over a 12 month period by a world class team. This project will establish the infrastructure to deliver an international precision medicine platform trial for ARDS. Dissemination will take multiple routes including publication in international journals, presentation at relevant national and international conferences, communication with participant and family networks as well as through social media and the lay press. Learning from this project will be shared as a template for future precision medicine trials in critical care.

Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: RESPIRATORY