A Phase 4 interventional study of Furosemide Injection and Isosorbide Dinitrate in Pulmonary Edema, Congestive Heart Failure and Acute Heart Failure, sponsored by Copenhagen University Hospital, Rigshospitalet. Recruiting at 5 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-23.
Sponsored by Copenhagen University Hospital, Rigshospitalet · Phase 4, Interventional, and Treatment
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.
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.
126 studies on the registry are indexed under Pulmonary Edema; 27 are open to participants now.
This study's planned enrollment of 1,041 is above the median of 65 across 62 interventional studies indexed under Pulmonary Edema.
Browse Pulmonary Edema studies →Copenhagen University Hospital, Rigshospitalet is the lead sponsor of 42 studies on the registry; 17 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Signs or suspicion of congestion (peripheral edema, rales, and/or clinical suspicion of congestion) *
Exclusion criteria
Exclusion criteria are purposely liberal, so patients can be included in accordance with everyday clinical practice. However, a safety criterion will be implemented:
If blood pressure drops below 90 mmHg in 2 measurements with 5 minutes apart and/or if urine production is below 50 ml after 1 hour, the intervention will be stopped, and patients can receive furosemide and nitrates freely.
We purposely chose not to exclude patients with aortic stenosis, since observational studies did not find excess risk of given nitrates to patients with pulmonary edema and aortic stenosis
Intravenous boluses of 40 mg furosemide with matching nitrate placebo, starting as soon as possible after inclusion and repeated up to ten doses at the treating physician's discretion during the six-hour intervention period. At least five minutes between doses and no more than three doses in the first 20 minutes. Protocol-specified response and safety criteria apply. Other usual care continues, and the intervention may be stopped early when open-label treatment is clinically required.
Drug: Furosemide Injection
Intravenous boluses of 3 mg isosorbide dinitrate with matching furosemide placebo, starting as soon as possible after inclusion and repeated up to ten doses at the treating physician's discretion during the six-hour intervention period. At least five minutes between doses and no more than three doses in the first 20 minutes. Protocol-specified response and safety criteria apply. Other usual care continues, and the intervention may be stopped early when open-label treatment is clinically required.
Drug: Isosorbide Dinitrate
Intravenous boluses of 40 mg furosemide together with 3 mg isosorbide dinitrate, starting as soon as possible after inclusion and repeated up to ten doses at the treating physician's discretion during the six-hour intervention period. At least five minutes between doses and no more than three doses in the first 20 minutes. Protocol-specified response and safety criteria apply. Other usual care continues, and the intervention may be stopped early when open-label treatment is clinically required.
Drug: Furosemide and isosorbide dinitrate
A diuretic (iv furosemide) strategy for decongestion in acute heart failure
Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure
Drug pages: Furosemide · 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
Days alive and outside hospital
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.
Time frame: 30 days
Intensification of therapy defined as at least one of: mechanical ventilation, renal replacement therapy, vasopressors, inotropes, or mechanical heart failure treatment.
Time frame: 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.
Time frame: 30 days
NT-proBNP at days 1-3
Time frame: Days 1-3 after inclusion
Early Warning Score measured 6-24 hours after start of intervention.
Time frame: 6-24 hours after start of intervention
Adverse events
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
Time frame: First 24 hours after inclusion
Patient-reported change in dyspnoea
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.
Time frame: 12-24 hours after inclusion
Echocardiographic substudy
parameters at day 0-3: LVEF, TAPSE, TR-gradient, VCI-size and compressibility, e/é. At Hvidovre and Bispebjerg sites, a transthoracic echocardiography will be performed at 12-72 hours after randomization. o Multiple B-lines in at least two areas on lung ultrasound identifying interstitial syndrome (yes/no) after 12-72 hours.
Time frame: 72 hours
Research biobank-parameters
IL-6, IL-10, copeptin, Soluble CD146 \[43\], carbohydrate antigen-125 \[44\], adrenomedullin \[45\], NT-proBNP \[46\], Neutrophil gelatinase-associated lipocalin (NGAL) \[47\]. Several biomarkers will be analyzed from the research biobank. Blood will be collected at admission day 1 (T24). The research biobank will be analyzed for biomarkers of inflammation, organ injury and other organ specific markers. The research biobank will only be collected at Bispebjerg and Hvidovre sites.
Time frame: 24 hours
FiO2, Blood pressure, respiratory rate, heart rate after 1 hour
Time frame: 1 hours
Myocardial infarction within 48 hours
Assessed by the treating clinician
Time frame: 2 days
FiO2, Blood pressure, respiratory rate, heart rate after 6 hours
Time frame: 6 hours
Number of patients where intervention is terminated (opt out) before 6 hours
Time frame: During the first 6 hours after inclusion
All-cause mortality,
Time frame: 30 days
Days alive out-of-ICU
Time frame: Day 30
Change from inclusion to t24 in creatinine and CRP at the next day after inclusion.
Time frame: 24 hours
Acute haemodynamic substudy: change in National Early Warning Score (NEWS)
Change in NEWS over the first 360 minutes in an embedded substudy of 79 participants from the main trial. NEWS comprises respiratory rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness, temperature and supplemental oxygen treatment. The substudy baseline (T0) is the first intravenous study-drug administration. This is the main outcome of the haemodynamic substudy; the main trial primary outcome remains days alive and outside hospital through day 30. Substudy participation depends on clinical suitability, feasibility and availability of trained staff and equipment.
Time frame: Baseline (first intravenous study-drug administration) to 360 minutes
Not enrolling at this site.
Plan to share: No
Started Sep 2023 (actual). Primary completion is estimated for May 2027, 43 months after the start.
Since we started tracking on Sep 25, 2026, the dates moved once, on Oct 23, 2026: primary completion Jun 2027 → May 2027 and completion Jun 2027 → May 2027.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Furosemide · Isosorbide Dinitrate
Copenhagen University Hospital, Rigshospitalet