DECONGEST-AHF: Vasodilatation or Loop Diuretics in Acute Heart Failure

DECONGEST-AHF is an investigator-initiated, randomised, double-blind, placebo-controlled, multicentre trial comparing initial intravenous loop-diuretic treatment, nitrate treatment, and their combination in adults with suspected pulmonary congestion due to acute heart failure. Treatment starts within three hours of hospital admission. Participants are allocated 1:1:1 to furosemide plus nitrate placebo, isosorbide dinitrate plus furosemide placebo, or both active treatments.

INTERVENTION The intervention period lasts six hours from inclusion, defined as opening the pre-randomised study box. Each dose consists of 40 mg intravenous furosemide or matching placebo together with 3 mg intravenous isosorbide dinitrate or matching placebo. Up to ten doses may be administered at the treating physician's discretion, with at least five minutes between doses and no more than three doses during the first 20 minutes. Protocol-specified response and safety criteria guide subsequent administration. The treating physician may stop the assigned intervention whenever additional open-label nitrates or loop diuretics are needed; after six hours these treatments may be used freely. Other usual care is provided throughout.

The pre-randomisation exclusion threshold is more than 50 mg intravenous furosemide in the preceding three hours, including prehospital treatment. This threshold does not change the 40 mg furosemide dose used for the trial intervention.

OUTCOMES AND SAMPLE SIZE The primary outcome is days alive and outside hospital during the 30 days after the index emergency-department visit. An emergency-department return counts as one hospital day. The planned sample size is 1,041 participants (347 per group), based on TAP-IT outcome data and simulations using the Zhao approximation with the van Elteren test, five sites and three pairwise comparisons. The protocol uses a Bonferroni-adjusted two-sided significance level of approximately 0.017 per comparison. Under the stated assumptions, including a one-day difference in days alive and outside hospital and a 15% relative reduction in mortality, estimated power is 81.1%.

ACUTE HAEMODYNAMIC SUBSTUDY Protocol version 4.1 adds an embedded substudy of 79 participants already enrolled in DECONGEST-AHF. Selection requires that additional measurements are clinically feasible and safe, trained staff and equipment are available, and procedures are not inappropriate or overly burdensome. Not every main-trial participant will be offered participation.

Repeated bedside assessments extend from baseline to 360 minutes; substudy T0 is defined as administration of the first intravenous study drug. Measurements include National Early Warning Score (NEWS), blood pressure, perfusion index, dyspnoea on a five-point Likert scale, focused lung ultrasound, arterial blood gases, venous blood analyses and echocardiography (E/e', tricuspid regurgitation gradient, inferior vena cava and left ventricular outflow tract velocity-time integral). The substudy evaluates change in NEWS over the first 360 minutes. It does not introduce a new treatment allocation or replace the main trial's 30-day primary outcome.

CONSENT AND FOLLOW-UP The protocol provides for emergency inclusion of eligible incapacitated patients, followed by the applicable approved consent procedures without undue delay. These involve a trial guardian and next of kin where required and the participant when capacity is regained. The participant's decision takes precedence once capacity is regained. Main-trial follow-up is through day 30.

PROTOCOL UPDATE This description reflects protocol version 4.1 and substantial modification SM-8, authorised in Denmark on 28 January 2026. The principal changes are the pre-randomisation furosemide threshold, the haemodynamic substudy and the revised sample-size calculation.