Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN)

Background: Many survivors of novel coronavirus infections (SARS-Cov and MERS-Cov) had substantial physical, psychological and neurological morbidity for up to 12 months. Similar longer-term consequences of COVID-19 are now apparent. Case level mental health diagnoses along with disabling fatigue, breathlessness and muscle weakness are commonly reported. There is a large population of COVID-19 survivors in the UK with persistently reduced quality of life, even after several months of recovery. Exercise and psychological rehabilitation may help but existing NHS rehabilitation services have insufficient capacity. Alternative delivery models must be tested. Design/setting: Two-arm multi-centre RCT with parallel process evaluation and 1-month internal pilot (n=35). Treatment allocation of 1:1.03 randomised by minimisation based on age, assisted ventilation, and case level mental health disorder. Population: Adults recovering from COVID-19, more than 3 months after hospital discharge with continued physical and/or mental health sequelae, and access to internet video. Exclusions are exercise contraindications and severe mental health problems preventing engagement. Health Technology Assessment: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN' (REGAIN) intervention is an eight-week, on-line, supervised, home-based, exercise rehabilitation programme with behavioural, motivational and mental health support. REGAIN includes: 1) individual assessment; 2) supervised home-based exercise programme with pre-recorded and live sessions; 3) one-to-one and group on-line psychosocial and motivational support and education. Control: Single, on-line, one-to-one, practitioner consultation with general advice on safe and effective physical activity. Outcomes. All measures completed on-line at baseline and 3 (post-intervention), 6- and 12-months post-randomisation. Primary: PROMIS® 29+2 Quality of Life questionnaire at 3 months. Secondary: dyspnoea, EQ-5D-5L, anxiety/depression, PTSD symptom severity, cognitive function, work status, physical activity, health and social care use, cost-effectiveness. Sample size: Allowing for 10% loss to follow-up, 535 (263 control, 272 intervention) participants are required to achieve 90% power at 5% significance level; based on standardised mean effect size of 0.3 (i.e. three points), intervention group size of 8 and an intra cluster coefficient of 0.01. Analysis. Summarised/reported as per CONSORT, using intention-to-treat analyses. Treatment effects (with 95% CI) estimated with hierarchical linear regression models, adjusted for patient-level covariates. We will estimate and adjust for site effects as a random variable in the model. Categorical data analysed using logistic regression models. Pre-specified, exploratory sub-group analyses will examine the interaction of treatment assignment. Prospective cost-effectiveness assessed as incremental cost per QALY estimates and credible intervals, cost-effectiveness acceptability curve and value-of-information analyses. Team: Lay partners, ICUsteps charity, clinical exercise physiology, physiotherapy, health psychology, psychiatry, critical care and respiratory medicine, general practice, statistics, health economics, clinical trialists. Timeline (month): set-up (0-1); internal pilot (2-3); recruitment (2-9); primary outcome (5-12); analysis/dissemination (13-14), 6-month follow-up (8-15), 12-month follow-up (15-22).