Johannes Grand - Postdoctoral Fellowship 2022

Project summary:
A randomized placebo-controlled trial for improving treatment of pulmonary edema

Acute heart failure is a condition of severe dyspnea requiring hospitalization. Central in the acute treatment is reduction of cardiac and systemic blood pressures with nitrates and/or diuretics. However, these treatments have never been investigated in the emergency department in the first hours of hospitalizations. The purpose of this study is to determine the efficacy of diuretics, nitrates or the combination in patients with acute heart failure. We plan a randomized, placebo-controlled trial with 1000 patients.

Project Title

Vasodilation or diuretics for initial treatment of pulmonary congestion due to acute heart failure – a randomized placebo-controlled trial


Loop diuretics have been a key component in treating pulmonary edema since the nineteen sixties. On the other hand, vasodilation was downgraded in European guidelines in 2021 for the treatment of acute heart failure due to a lack of trials that compare vasodilation with loop-diuretics in an acute clinical setting. We propose to investigate this clinical equipoise in a trial including patients immediately at hospital admission.


To determine the superior strategy of loop-diuretics (furosemide), vasodilation (nitrates) or the combination during emergency treatment.


Randomized, placebo-controlled trial with 1:1:1 allocation. The three strategies will be: 1. Boluses of 40 mg IV furosemide, 2. Boluses of 3 mg IV isosorbide dinitrate, or 3: The combination of the two strategies.

We consider a reduction in days alive and outside the hospital to day 30 of at least 1 day as the minimal significant difference. To have 80 % power to find this difference with a standard deviation of 5, we need to include 1104 patients. The alphalevel is 0.05, and the betalevel is 20 %. We expect minimal dropouts. The study will include patients over an estimated period of 2.5 years.

Johannes Grand

  • MD and PhD 
  • Copenhagen University Hospital, Bispebjerg Hospital, Cardiac Department


Professor Olav W. Nielsen, Bispebjerg Hospital