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Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload

ConditionAcute Heart Failure
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorJohannes Grand

About this trial

Aim to identify the best strategy for treating acute heart failure (AHF) with volume overload, particularly focusing on patients resistant to standard loop-diuretics. The trial is a double-blinded, randomized, controlled, multicenter study. Its primary objective is to compare the efficacy of loop-diuretics combined with either Metolazone or Acetazolamide, against loop-diuretics alone. The trial will also determine the optimal type of loop-diuretic to use.

Eligible participants include adults over 18 years hospitalized with AHF and volume overload, showing signs of congestion and at risk of diuretic resistance. Exclusions apply to those with acute coronary syndrome, low systolic blood pressure, prior renal therapy, or previous treatment with Acetazolamide or Metolazone.

The primary outcome is the number of days alive and out-of-hospital by day 30. Secondary outcomes include a composite clinical benefit at 30 days, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and successful decongestion 72 hours post-inclusion.

The trial aims to enroll about 1,041,939 patients across three treatment arms over three years. The minimal important difference is set as a reduction in out-of-hospital days by at least two days, with an anticipated low dropout rate. The study's power is calculated to be 80% with an adjusted alpha level for comparing the three diuretic groups.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years

Acute hospital admission with a clinical diagnosis of acute heart failure with volume overload.

Daily loop-diuretics administration for a minimum of 7 days before admission, or

Insufficient decongestion observed in the preceding 24 hours (weight reduction <500g or negative fluid balance <1L) despite being treated with high-dose IV loop diuretic (equivalent to ≥120 mg IV furosemide within 24 hours).

Disqualifiers

Acute coronary syndrome

Systolic blood pressure <85 mmHg

Use of renal replacement therapy or ultrafiltration in-hospital before study inclusion

Treatment with acetazolamide or metolazone during the index hospitalization prior to randomization

Trial design

Design model

Parallel

Treatments tested in this trial

  • Acetazolamide

    Drug

    1\. 500 mg IV bolus of acetazolamide at randomization (day 0) and repeated the next 3 mornings (day 1, day 2 and day 3). This arm will also receive a placebo- Metolazone tablet together with each acetazolamide-injection.

  • Metolazone 2.5 MG

    Drug

    2\. 2.5 mg oral Metolazone at randomization (day 0) and repeated the next 3 mornings (day 1, day 2 and day 3). This arm will also receive a placebo- acetazolamide injection together with each metolazone-tablet.

  • Double-placebo

    Other intervention

    This arm will also receive both a placebo-acetazolamide injection together with a placebo-metolazone-tablet at randomization and repeated the next 3 mornings (day 1, day 2 and day 3).

Treatment groups

939 Participants
are divided into 3 treatment groups
Group A: AcetazolamideActive comparator 1 intervention
Group B: MetolazoneActive comparator 1 intervention
Group C: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Days alive out-of-hospital to day 30

Days alive out-of-hospital to day 30

Time frame
30 days

Secondary outcomes

1

Win ratio of 1. all-cause death, 2. Readmisison, 3. renal-replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥200% of the baseline value), assessed using a Hierarchical win-ratio' approach.

Number of Clinical benefit at 30 days, consisting of a composite of 1. all-cause death, 2. Readmisison after discharge from initial hospitalization, 3. new receipt of renal-replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥200% of the baseline value), assessed using a Hierarchical win-ratio' approach.

Time frame
30 days
2

Kansas City Cardiomyopathy Questionnaire

Kansas City Cardiomyopathy Questionnaire (KCCQ). Minimum and Maximum Values: The KCCQ is scored on a scale from 0 to 100. Interpretation of Scores: Higher Scores: Indicate better heart failure-related quality of life, fewer symptoms, and fewer physical and social limitations. Lower Scores: Suggest more severe heart failure symptoms, greater physical limitations, and a poorer quality of life.

Time frame
30 days
3

Decongestion score 72 hours after inclusion

scale from 0 to 10 on the basis of the sum of scores for the degree of edema (0 to 4), pleural effusion (0 to 3), and ascites (0 to 3), with higher scores indicating a worse condition on all scales

Time frame
72 hours

Other outcomes

Sponsors and contacts

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

Johannes Grand

Lead sponsor

Copenhagen University Hospital, Hvidovre

Sponsor institution

Source ClinicalTrials.gov
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