RT Journal Article SR Electronic T1 Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients JF BMJ Open JO BMJ Open FD British Medical Journal Publishing Group SP e076519 DO 10.1136/bmjopen-2023-076519 VO 14 IS 2 A1 Shiraishi, Yasuyuki A1 Ikemura, Nobuhiro A1 Urashima, Mitsuyoshi A1 Kohno, Takashi A1 Nakano, Shintaro A1 Tanaka, Toshikazu A1 Nagatomo, Yuji A1 Ikoma, Takenori A1 Ono, Tomohiko A1 Numasawa, Yohei A1 Sakamoto, Munehisa A1 Nishikawa, Kei A1 Takei, Makoto A1 Hakuno, Daihiko A1 Nakamaru, Ryo A1 Ueda, Ikuko A1 Kohsaka, Shun YR 2024 UL http://bmjopen.bmj.com/content/14/2/e076519.abstract AB Introduction The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects.Methods and analysis In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients’ QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients’ health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint.Ethics and dissemination The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses.Trial registration number UMIN000045229