NCT05276219

Optimized Treatment of Pulmonary Edema or Congestion

Vasodilation or Loop-diuretics for Initial Treatment of Pulmonary Edema or Congestion Due to Acute Heart Failure - a Randomized Placebo-controlled Trial

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1,104 (estimated)
• Sponsor: Johannes Grand · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: 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

IV-loop diuretics are a central part of acute treatment of pulmonary edema and is recommended in guidelines (Class 1 recommendation) with a higher recommendation as compared to vasodilation, which was downgraded from Ia to IIb in the 2021 guidelines for heart failure. However, the effects of loop-diuretics alone or in combination with nitrates compared to nitrates alone is unknown and should be investigated in adequately powered prospective trials to optimize acute treatment of these patients. 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

• Pulmonary Edema
• Congestive Heart Failure
• Acute Heart Failure

Interventions

Type	Name	Description
DRUG	Furosemide Injection	A diuretic (iv furosemide) strategy for decongestion in acute heart failure
DRUG	Isosorbide Dinitrate	Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure
DRUG	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

Timeline

• Start date: 2023-09-14
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2022-03-11
• Last updated: 2024-12-19

Locations

4 sites across 1 country: Denmark