ABSTRACT
Background: Water retention leading to worsening congestion is a common reason for heart failure (HF) hospitalisation. Increases in aldosterone, due to increased secretion (driven by angiotensin and hyperkalaemia) and reduced degradation (due to hepatic dysfunction), contribute to congestion. Mineralocorticoid receptor antagonists (MRA) reduce morbidity and mortality in advanced HF. However, use of MRA is often limited by hyperkalaemia, renal dysfunction and hypotension. Hyperkalaemia can be corrected by potassium binding agents. Methods: An open-label, randomised, multi-centre (up to 100 UK sites) trial investigating the use of a potassium binding agent, patiromer, to facilitate higher doses of MRA for HF with worsening congestion requiring treatment with ≥80mg/day of furosemide (or equivalent). Patients are first entered on an unconsented screening-log (approved by the UK Health Research Authority) and then asked to consent to a registry (no exclusion criteria). If they agree, and are eligible (systolic blood pressure ≥90mmHg, eGFR ≥30mL/min/1.73 m2, no other terminal disease, no active infection or myocardial ischaemia), they are invited to participate in a randomised trial. Patients who consent for the trial enter a run-in phase of ≤35 days, when they receive ≤100mg/day of spironolactone. If serum potassium rises to >5.0mmol/L, the patient is randomised either to receive an MRA at guideline recommended doses or to have spironolactone increased ≤200mg/day, using patiromer to manage hyperkalaemia, providing eGFR remains ≥30mL/min and the patient does not become hypotensive. The primary outcome of the first phase of the trial (n = 400) is severity of congestion at 60-days but patients will be followed The RELIEHF Registry & Randomised Trial long-term for morbidity and mortality. An adaptive trial design allows recruitment to be increased up to 2.000 patients. Results: The conduct of the trial has been disrupted by COVID. As of January 2022, from 10 sites, >300 patients (40% women;median age 76 (65-83) years have been screened, >100 (37% women;median age 72 (62-80) years) have consented for the registry and >25 for the randomised trial. Of patients screened, about 50% were asked for registry-consent, of whom one third refused. The main reason for not asking was that the care-team considered it inappropriate due to patient frailty and/or cognitive dysfunction. Most patients who consented for the registry agreed, in principle, to participate in a randomised trial. Most patients have tolerated 100mg of spironolactone during the run-in period. Conclusions: For a high proportion of patients admitted to hospital with worsening HF, research staff do not deem it appropriate to approach them to ask for research consent. Most patients with HF who were asked to participate in research were willing to do so and to participate in a randomised trial, although a substantial proportion were not eligible for this trial. Of those who were, the majority tolerated spironolactone at a dose of 100mg/day.
ABSTRACT
BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.