Every year, one in four patients discharged after hospital treatment for heart failure is readmitted or dies within 30 days, often because fluid congestion was not adequately controlled. This preparatory study aims to design a large clinical trial that will test whether adding a second drug—such as acetazolamide, a thiazide, digoxin, oral sodium chloride, or a glucocorticoid—to the standard diuretic furosemide can improve outcomes for these patients. Heart failure hospitalisations cost the UK roughly £2 billion annually, and current treatment with intravenous furosemide alone frequently causes side effects and relapse. The researchers will conduct a rapid review of existing evidence, survey clinicians on which adjuncts are most acceptable, and convene expert and patient panels to decide on drug doses, treatment duration, and trial endpoints. They will also run statistical simulations to determine the most efficient trial design. If the subsequent multi-arm, multi-stage trial succeeds, it could shorten hospital stays, reduce the need for high-dose diuretics, and lower readmission and death rates. That would directly improve patients’ quality of life and reduce pressure on NHS hospitals and budgets.
View original technical description
Research question Which adjunctive therapies improve the clinical response to loop diuretics in patients admitted to hospital with heart failure (HF) and does this lead to better outcomes? Background Worsening congestion (water retention) is a common cause of hospitalisations for HF, accounting for most of the estimated ~£2 billion per year spent on managing HF in the UK.1-3 Within 30 days of discharge, 1 in 4 patients will be readmitted or die, often due to inadequate control of congestion.3,4 Intravenous (IV) furosemide is the current mainstay for the initial treatment of severe congestion, but side effects of treatment, and relapse are common.5 Combining furosemide with adjunctive therapies during admission and after discharge might 1) shorten length of hospitalisation; 2) reduce loop diuretic requirements; 3) improve symptoms; and 4) reduce rates of readmission or death. Possible oral adjuncts to loop diuretic include acetazolamide, thiazides, digoxin, oral sodium chloride, and glucocorticoids.6 This research proposal will inform the design of a multi-arm, multi-stage (MAMS) randomised trial of each adjunct alongside furosemide in patients admitted with severe congestion due to heart failure. Aims and Objectives Choose which adjunctive therapies, at what dose, and for how long Choose the dose(s) of IV furosemide to be used as the comparator Choose primary and secondary outcomes Estimate recruitment and engage sites for a future trial Estimate sample size and develop the statistical framework for a MAMS trial The primary objective is to submit a stage 1 application for the MAMS trial to the NIHR HTA. Methods Work-package 1 (WP1) 1) a rapid review of the efficacy of oral corticosteroid and sodium chloride supplements (acetazolamide, thiazides, and digoxin already feature in HF guidelines).7 2) an umbrella review of the long-term safety of proposed adjunctive therapies (except digoxin which is commonly used long-term in patients with HF). WP2a 1) An online survey of clinicians (doctors, nurses and pharmacists) assessing potential ability to recruit and the acceptability of each adjunct and willingness to support a trial. 2) Evidence generated (survey and reviews) will be considered by an expert panel (N=20-25) including expert clinicians and allied health professionals who care for people with HF using a modified Delphi approach. The panel will make recommendations on all aspects of the trial design. 3) A patient and carer panel of people with a recent hospitalisation (<6 months) for HF will provide recommendations on trial endpoints. The patient-and-carer advisory group (PCAG) will also input into these discussions. WP2b Statistical simulations of possible MAMS designs. The grant application will be co-developed with the PCAG. Timelines for delivery WP1 – months 1-8; WP2a months 8-12; WP2b months 9-15. Anticipated Impact and Dissemination This topic is identified as of high importance by the patient-led James Lind Alliance, the European Society of Cardiology, and the National Institute of Health and Care Excellence. This proposal will collect the information needed to launch an efficient clinical trial and will enhance our understanding of attitudes toward hospitalisation and treatment. Results will be disseminated across patient groups, conferences, and in peer-reviewed journals.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know