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
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