HElping Alleviate the Longer-term consequences of COVID-19 (HEAL-COVID): A national platform trial

Research question: Can interventions in the convalescent phase of COVID-19 improve longer-term outcomes? Background: COVID-19 is a new disease for which the natural history remains uncertain. However, recent data suggest that >10% of patients die and >25% of patients require readmission to hospital within 4 months of discharge. A unique feature of COVID-19 is the high incidence of cardiovascular and pulmonary complications including venous thromboembolism, persistent lung inflammation, and pulmonary fibrosis; These may not be confined to the acute phase of the illness, but rather may also occur during the convalescent phase of the illness, thus providing a major contribution to the ill-defined syndrome 'Äúlong COVID'Äù. Aims and objectives: The primary aim of the proposal is to set up a pragmatic phase 3 adaptive clinical trial platform designed to provide reliable evidence on the efficacy of post-hospitalisation treatments aiming to improve clinical outcomes from COVID-19. Methods: We propose to establish a clinical trial platform, integrated into the current national COVID-19 clinical characterisation (ISARIC4C, GenoMICC, PHOSP-C) and acute clinical trial landscape (RECOVERY, REMAP-CAP, PRINCIPLE). The platform will be an pragmatic open-label adaptive trial, with the flexibility to add intervention arms as evidence from partner studies emerges. The primary endpoint of the trial will be hospital free survival at 12 months after randomisation, and will be assessed using linkage to routinely collected clinical data via NHS Digital. Secondary endpoints will include patient reported outcome measures (based on Core Outcome Sets for COVID-19 and long-term follow up for pattens with acute respiratory failure) and quality of life assessment. Timelines for delivery: Study set-up will run in parallel with this grant application and with a planned start date of March 2021. The study is proposed as a UK-wide national Urgent Public Health platform trial; set-up to close-down is projected to take three years. Anticipated impact and dissemination: The aim of the trial is to change the standard of care for patients with COVID-19 by determining which interventions do and do not alter longer-term clinical outcomes. We propose to disseminate the outputs of the study to both patient and public audiences, as well as healthcare audiences via open access peer reviewed publications, presentations to conferences as well as patient/participant groups, press releases (where appropriate), social media, and clinical management guidelines. In addition we aim to establish an online digital patient community to ensure the findings of our work are effectively shared with people who experience Long COVID.