Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE4
1104 participants
INTERVENTIONAL
2023-09-14
2026-12-31
Brief Summary
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Intravenous (IV) loop-diuretics have been a key component in treating pulmonary edema since the nineteen sixties and has a Class 1 recommendation in the 2021 European Society of Cardiology guidelines for heart failure. Conversely, vasodilation was downgraded in the treatment of acute heart failure due to a lack of trials that compare vasodilation with loop-diuretics in a hyperacute clinical setting. This clinical equipoise will be tested in a trial including patients with pulmonary congestion immediately at hospital admission.
Primary objective:
To determine the superior strategy of loop-diuretics (furosemide), vasodilation (nitrates) or the combination during emergency treatment.
Design: Investigator-initiated, randomized, double-blinded, placebo-controlled trial with 1:1:1 allocation.
Intervention:
Intervention-phase will last 6 hours from study-inclusion, and patients will be allocated to one of three groups:
* Boluses of 40 mg IV furosemide + nitrate-placebo as soon as possible and repeated up to 10 times.
* Boluses of 3 mg IV isosorbide dinitrate + furosemide-placebo as soon as possible.
* Boluses of both 3 mg IV isosorbide dinitrate + of 40 mg as soon as possible.
Detailed Description
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Trial objective The primary objective is to determine the superior strategy of urgent treatment (starting within 3 hours after hospital-admission) of pulmonary edema. Strategies are: 1. Diuretics (Furosemide), 2. Vasodilation (nitrates), 3. A combination of both furosemide and nitrates. Patient-outcome will be evaluated through the primary endpoint as described elsewhere.
Hypothesis:
Iv nitrates in combination with iv furosemide are superior compared to iv furosemide alone or iv nitrates alone during initial (first 6 hours) in-hospital treatment of pulmonary edema. "Superior" is defined as a significant benefit on the primary outcome.
Study design The study is an investigator-initiated, randomized, placebo-controlled, double-blinded, multicenter, interventional, clinical trial. Following successful completion of screening procedures, patients will be randomized in a 1:1:1 fashion to receive either of the 3 treatments-strategies.
Since patients are in cardio-respiratory and mental stress, informed consent prior to the intervention will be impossible. Instead, a legal guardian will be contacted and asked for consent in addition to next of kind and patients regaining mental ability.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
* 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.
TREATMENT
QUADRUPLE
Study Groups
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Furosemide only
• Boluses of 40 mg furosemide given as soon as possible and repeated up to 10 times by the discretion of the treating physician.
Furosemide Injection
A diuretic (iv furosemide) strategy for decongestion in acute heart failure
isosorbide dinitrate
• 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.
Isosorbide Dinitrate
Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure
isosorbide dinitrate + furosemide
• 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.
Furosemide 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
Interventions
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Furosemide Injection
A diuretic (iv furosemide) strategy for decongestion in acute heart failure
Isosorbide Dinitrate
Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure
Furosemide 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
Eligibility Criteria
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Inclusion Criteria
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
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.
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
18 Years
ALL
No
Sponsors
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Zealand University Hospital
OTHER
Copenhagen University Hospital, Hvidovre
OTHER
Bispebjerg Hospital
OTHER
Johannes Grand
OTHER
Responsible Party
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Johannes Grand
Principal investigator
Principal Investigators
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Johannes Grand, PhD
Role: PRINCIPAL_INVESTIGATOR
Hvidovre University Hospital
Locations
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Bispebjerg Hospital
Copenhagen, Copenhagen, Denmark
Hvidovre Hospital
Copenhagen, Copenhagen, Denmark
Nordsjællands Hospital
Hillerød, , Denmark
Roskilde Hospital
Roskilde, , Denmark
Countries
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Central Contacts
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Facility Contacts
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Jens Jakob Thune, MD, PhD
Role: primary
Jens Jakob Thune
Role: backup
Johannes Grand, MD, PhD
Role: primary
Johannes Grand, MD, PhD
Role: backup
Søren Junge, MD
Role: primary
Søren Junge, MD, PhD
Role: backup
Matias Lindholm
Role: primary
Matias Lindholm, MD, PhD
Role: backup
Other Identifiers
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2022-500035-36-01
Identifier Type: OTHER
Identifier Source: secondary_id
08102021_ver2.5
Identifier Type: -
Identifier Source: org_study_id