The effectiveness and cost effectiveness of COenzyme Q10 in heaRt fAiLure with reduced ejection fraction (CORAL): a pragmatic, patient-centred, data-enabled trial in primary care

RESEARCH QUESTION: In patients with heart failure (HF) with reduced ejection fraction (HFrEF; EF <50%), is the addition of CoQ10 to usual care effective and cost-effective? BACKGROUND: HF is long-term condition that causes breathlessness, fatigue and leg swelling, which markedly impair quality of life (QoL). Improving QoL is a priority for people with HF. OBJECTIVES: To estimate the difference between groups in the primary endpoint of HF specific Health Related Quality of Life (HRQoL) and the following secondary endpoints: all cause and cardiovascular death; all cause and cardiovascular hospitalisation; major adverse cardiovascular events (MACE); self-assessed NYHA functional classification; QoL assessed using EQ-5D-5L; costs; adherence. METHODS: Design: Pragmatic, patient-centred, data enabled, placebo-controlled randomised controlled trial (RCT), with internal pilot and economic evaluation. To minimise research burden, recruitment, consent and collection of patient-reported outcomes will be done remotely (via online questionnaires or telephone). Setting: Primary care. Population: Adults with HFrEF, identified from electronic GP records using standardised diagnosis codes for HF and left ventricular systolic dysfunction (LVSD) or electronic / manual record searches for evidence of LVSD. Inclusion criteria: Aged >=18, evidence in GP record of LVSD, and NYHA class >=II. Exclusion criteria: diastolic dysfunction with EF>50% or preserved left ventricular function; NYHA class I, current use of CoQ10, allergy to CoQ10, warfarin use, unable to provide informed consent. Interventions: CoQ10 (ubiquinone) 300mg/d (one 100mg dose, three times daily) or placebo (three times daily) for 12 months in addition to usual care. Outcomes: Primary: HF specific HRQoL assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary: all cause and cardiovascular death; all cause, cardiovascular and HF hospitalisation; major adverse cardiovascular events (MACE); self-assessed NYHA functional classification; QoL assessed using EQ-5D-5L questionnaire; costs; adherence. Major secondary endpoint: Combined hierarchical endpoint incorporating all cause death, all cause hospitalisation and KCCQ clinical summary score analysed using the win ratio method. Sample size: 950 participants (475 in each group) will allow us to detect a 3-point difference (standard deviation 19) in the overall clinical summary score of the KCCQ with 90% power and a 2-sided alpha of 0.05, assuming a correlation between baseline and follow-up of 0.46, correlation between repeat follow up scores 0.68 and a 5% loss to follow up. TIMELINE FOR DELIVERY (total 42 months): 8 months set-up; 14 months recruitment (of which 6 months internal pilot); 12 months follow-up; 2 months data cleaning / formatting; 6 months analysis/reporting. ANTICIPATED IMPACT AND DISSEMINATION: If effective, CoQ10 has the potential to improve QoL for people with HF. Our pragmatic design will produce generalisable evidence to facilitate implementation. Study findings will be disseminated using targeted approaches for different stakeholder groups including people with HF and their carers, GPs and primary care nurses, cardiologists, HF specialist nurses and medicine management teams.