Health TrialsbyHealthPanel

Optimized Treatment of Pulmonary Edema or Congestion

ConditionsPulmonary EdemaCongestive Heart FailureAcute Heart Failure
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorRigshospitalet, Denmark

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

This trial does not accept healthy volunteers

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

Design model

Parallel

Treatments tested in this trial

  • Furosemide Injection

    Drug

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

  • Isosorbide Dinitrate

    Drug

    Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure

  • Furosemide and isosorbide dinitrate

    Drug

    Vasodilation (iv isosorbide dinitrate) strategy for decongestion in acute heart failure AND A diuretic (iv furosemide) strategy for decongestion in acute heart failure

Treatment groups

1,104 Participants
are divided into 3 treatment groups
Group A: Furosemide onlyActive comparator 1 intervention
Group B: isosorbide dinitrateActive comparator 1 intervention
Group C: isosorbide dinitrate + furosemideActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Days alive and outside hospital

The primary end point is the number of days alive and out of hospital during the 30-day period after the hospital-visit. The choice of this end point allow capturing the burden of acute heart failure in terms of mortality, hospital length of stay, and early readmission to the hospital. Patients who died before day 30 will be counted as having zero days alive and out of hospital. A return visit to the emergency department was considered as 1 day in the hospital, using the same approach as a recent trial of acute heart failure.

Time frame
30 days

Secondary outcomes

1

Intensification of therapy defined as at least one of: mechanical ventilation, renal replacement therapy, vasopressors, inotropes, or mechanical heart failure treatment.

Time frame
30 days
2

Clinical benefit at 30 days, consisting of a composite of 1. All-cause death, 2. Intubation with mechanical ventilation, and 3. rehospitalization, assessed using a 'win-ratio' approach.

Time frame
30 days
3

NT-proBNP at day 1-3

Time frame
30 days
4

Early Warning Score measured 6-24 hours after start of intervention.

Time frame
24 hours

Other outcomes

1

Echocardiographic substudy

parameters at day 0-3: LVEF, TAPSE, TR-gradient, VCI-size and compressibility, e/é. At Hvidovre and Bispebjerg sites, a transthoracic echocardiography will be performed at 12-72 hours after randomization. o Multiple B-lines in at least two areas on lung ultrasound identifying interstitial syndrome (yes/no) after 12-72 hours.

Time frame
72 hours
2

Research biobank-parameters

IL-6, IL-10, copeptin, Soluble CD146 \[43\], carbohydrate antigen-125 \[44\], adrenomedullin \[45\], NT-proBNP \[46\], Neutrophil gelatinase-associated lipocalin (NGAL) \[47\]. Several biomarkers will be analyzed from the research biobank. Blood will be collected at admission day 1 (T24). The research biobank will be analyzed for biomarkers of inflammation, organ injury and other organ specific markers. The research biobank will only be collected at Bispebjerg and Hvidovre sites.

Time frame
24 hours
3

FiO2, Blood pressure, respiratory rate, heart rate after 1 hour

Time frame
1 hours
4

Myocardial infarction within 48 hours

Assessed by the treating clinician

Time frame
2 days

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Rigshospitalet, Denmark

Lead sponsor

Hvidovre University Hospital

Sponsor institution

Zealand University Hospital

Collaborator

Copenhagen University Hospital, Hvidovre

Collaborator

Bispebjerg Hospital

Collaborator

Herlev Hospital

Collaborator

Source ClinicalTrials.gov
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