Pulmonary Edema, Congestive Heart Failure, Acute Heart Failure
Conditions
Keywords
acute heart failure, Pulmonary edema
Brief summary
DECONGEST-AHF compares three initial treatments for adults admitted with suspected pulmonary congestion due to acute heart failure: intravenous furosemide, intravenous isosorbide dinitrate, or both medicines together. The aim is to determine which treatment gives patients the most days alive and outside hospital during the first 30 days. The trial is investigator-initiated, multicentre, randomised and blinded, with 1,041 participants allocated equally to three groups. During the first six hours, participants receive repeated boluses of 40 mg furosemide with nitrate placebo, 3 mg isosorbide dinitrate with furosemide placebo, or both active medicines. Doses are repeated at the treating physician's discretion within the protocol limits. Other usual care continues, and treatment may be stopped early if clinically required. An embedded substudy will examine early clinical and haemodynamic responses in 79 participants from the main trial, using repeated bedside measurements during the first 360 minutes. The main trial treatment groups and primary outcome are unchanged.
Detailed description
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.
Interventions
A diuretic (iv furosemide) strategy for decongestion in acute heart failure
Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure
DRUGFurosemide and isosorbide dinitrate
Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure AND A diuretic (iv furosemide) strategy for decongestion in acute heart failure
Sponsors
Copenhagen University Hospital, Rigshospitalet
Zealand University Hospital
Copenhagen University Hospital, Hvidovre
Herlev Hospital
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching and identical placebo (saline)
Intervention model description
Inter-regional collaborative, randomized, placebo-controlled trial with 1:1:1 allocation * Boluses of 40 mg furosemide given as soon as possible and repeated up to 10 times by the discretion of the treating physician. * Boluses of 3 mg IV isosorbide dinitrate given as soon as possible and repeated up to 10 times by the discretion of the treating physician. * Boluses of both 3 mg IV isosorbide dinitrate + of 40 mg furosemide given as soon as possible and repeated up to 10 times by the discretion of the treating physician.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Acute (within minutes to days) onset or worsening of subjective dyspnea\* 3. Systolic blood pressure ≥100 mmHg 4. Oxygen saturation \<94% or need of oxygen 5. Signs or suspicion of congestion (peripheral edema, rales, and/or clinical suspicion of congestion) \* * by the best assessment from a medical doctor. Inclusion must not wait on x-ray or other measures: patients suspected of pulmonary congestion should be included immediately.
Exclusion criteria
1. More than 50 mg IV furosemide within the last three hours before randomization including prehospital treatment. 2. More than 3 hours from hospital-admission to randomization 3. Ongoing ventricular taky- or brady-arrythmias or supraventricular arrhythmias with HR \> 180 or \< 40 bpm. 4. Suspected severe infection or sepsis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days alive and outside hospital | 30 days | The number of days during the 30-day period after the index emergency-department visit that the participant is alive and outside hospital. The outcome captures mortality, duration of the index admission and subsequent hospital readmissions. A return visit to an emergency department is counted as one hospital day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intensification of therapy defined as at least one of: mechanical ventilation, renal replacement therapy, vasopressors, inotropes, or mechanical heart failure treatment. | 30 days | — |
| Clinical benefit at 30 days, consisting of a composite of 1. All-cause death, 2. Intubation with mechanical ventilation, and 3. rehospitalization, assessed using a 'win-ratio' approach. | 30 days | — |
| NT-proBNP at days 1-3 | Days 1-3 after inclusion | — |
| Early Warning Score measured 6-24 hours after start of intervention. | 6-24 hours after start of intervention | — |
| Adverse events | First 24 hours after inclusion | An adverse event means any untoward medical occurrence in a subject to whom a medicinal product is administered, and which does not necessarily have a causal relationship with this treatment. Adverse events (AE) will be categorized according to the definitions below. To assess specific adverse events possibly related to the trial intervention, we will collect data on the following during the first 24 hours after inclusion in the trial: Symptomatic hypotension requiring medical treatment Dialysis or renal replacement therapy Potassium below 2.5 mmol/L or above 6.0 mmol/L VF, VT or AF requiring DC conversion New need for pacing Intubation and mechanical ventilation Headache requiring treatment Hearing loss Anaphylaxis |
| Patient-reported change in dyspnoea | 12-24 hours after inclusion | Patient-reported change in dyspnoea compared with admission, assessed in a standardised position using a seven-point Likert scale: marked improvement = +3, moderate improvement = +2, slight improvement = +1, no change = 0, slight worsening = -1, moderate worsening = -2, and marked worsening = -3. Higher values indicate greater improvement. |
Countries
Denmark
Contacts
CONTACTJohannes Grand, MD, Phd, MPH
CONTACTJens Jakob Thune, MD, PhD
PRINCIPAL_INVESTIGATORJohannes Grand, PhD
Hvidovre University Hospital
Outcome results
None listed