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Introduction Heart failure (HF) is a leading cause of hospitalisation in older people. Most patients hospitalised with HF have profound congestion due to water & salt retention. Adverse outcomes after discharge are common: within a month, 1 in 4 are readmitted, and 1 in 8 will die.The cornerstone of treatment for severe congestion is intravenous (IV) loop diuretics; usually furosemide. However, a poor response to loop diuretics (diuretic resistance) is common especially when renal function is impaired. Combining loop diuretics with adjunctive treatments might increase diuresis, reduce complications (such as renal dysfunction), shorten hospitalisation, and improve the patient experience and outcomes. Continuing adjunctive treatments after discharge might reduce the risk of recurrent congestion and clinical relapse.A scoping review has identified 5 possible adjunctive treatments that could be started as an in-patient and continued after discharge (table 1).Abstract 5-010 Table 1 Adjunctive diuretic Suitable for MAMMOTH-HF Acetazolamide Yes Thiazide (and thiazide-like) diuretics Yes Digoxin Yes Corticosteroid Yes Hypertonic saline No – cannot be given after discharge Oral sodium chloride Yes Tolvaptan No – costly and logistically difficult to give in the UK Sodium glucose co-transporter 2 inhibitors No – foundational therapy for HF, cannot be withheld. Spironolactone No – foundational therapy for HF, cannot be withheld. Methods To assess whether any of these adjunctive therapies improve symptoms or outcome, we are planning a multi-arm, multi-stage randomised trial. Before such a trial can be designed, several uncertainties should be addressed: suitability and acceptability of the proposed adjunctive therapies to patients and clinicians; which adjuncts to use, at what dose, and for how long; definition of standard of care as the comparator; choice of primary and secondary endpoints, the minimal clinically important difference for each intervention, and the timepoint at which they should be measured; willingness and capacity of investigator-teams to take part; the sample size required and stop/go criteria for each arm of the proposed MAMs trial.We will address these uncertainties through 2 work-packages (WP) (figure 1). WP 1 will include rapid reviews of corticosteroids and oral sodium chloride in patients with HF; and an umbrella review of the safety of all proposed adjunctive diuretics. WP 2 will include online surveys, expert panel meetings, and patient involvement to select the interventions to test, the endpoints to measure, and the timeframe for the study.Abstract 5-010 Figure 1Results Preparatory work has been funded by the National Institute for Health and Care Research - Research for Patient Benefit program - NIHR207987. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Conclusion If funded, the MAMMOTH-HF will be the definitive trial of adjunctive diuretics in patients with severe congestion. Early engagement with clinical investigators at national events is integral to success of the project.