RecruitingPhase 4NCT05276219

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


Sponsor

Johannes Grand

Enrollment

1,104 participants

Start Date

Sep 14, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • Age ≥ 18 years
  • Acute (within minutes to days) onset or worsening of subjective dyspnea\*
  • Systolic blood pressure ≥100 mmHg
  • Oxygen saturation \<94% or need of oxygen
  • 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 Criteria6

  • More than 40 mg IV furosemide within the last three hours before randomization including prehospital treatment.
  • More than 3 hours from hospital-admission to randomization
  • Ongoing ventricular taky- or brady-arrythmias or supraventricular arrhythmias with HR \> 180 or \< 40 bpm.
  • 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

Interventions

DRUGFurosemide Injection

A diuretic (iv furosemide) strategy for decongestion in acute heart failure

DRUGIsosorbide Dinitrate

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


Locations(4)

Bispebjerg Hospital

Copenhagen, Copenhagen, Denmark

Hvidovre Hospital

Copenhagen, Copenhagen, Denmark

Nordsjællands Hospital

Hillerød, Denmark

Roskilde Hospital

Roskilde, Denmark

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NCT05276219


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