About this trial

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 criteria

Qualifiers

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

Disqualifiers

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.

Trial design

Treatments tested in this trial

  • Furosemide Injection
  • Isosorbide Dinitrate
  • Furosemide and isosorbide dinitrate

Treatment groups

1,104 Participants
are divided into 3 treatment groups

Locations

4
Bispebjerg Hospital2000, CopenhagenCopenhagen, Denmark
Hvidovre Hospital2650, CopenhagenCopenhagen, Denmark
Nordsjællands Hospital Hillerød Denmark
Roskilde Hospital Roskilde Denmark

Sponsors and collaborators

Rigshospitalet, Denmark

Lead sponsor

Hvidovre University Hospital

Sponsor institution

Zealand University Hospital

Collaborator

Copenhagen University Hospital, Hvidovre

Collaborator

Bispebjerg Hospital

Collaborator

Herlev Hospital

Collaborator