Clinical trial

Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload - A Randomized Clinical Trial

Name

DRAIN_AHF

Description

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.

Trial arms

Trial start

2024-04-01

Estimated PCD

2027-03-31

Trial end

2027-03-31

Status

Not yet recruiting

Phase

Early phase I

Treatment

Acetazolamide

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.

Arms:

Acetazolamide

Other names:

Standard of care including loop-diuretics

Metolazone 2.5 MG

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.

Arms:

Metolazone

Other names:

Standard of care including loop-diuretics

Double-placebo

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).

Arms:

Placebo

Size

939

Primary endpoint

Days alive out-of-hospital to day 30

30 days

Eligibility criteria

Inclusion Criteria: 1. Age ≥ 18 years 2. Acute hospital admission with a clinical diagnosis of acute heart failure with volume overload. 3. At risk of diuretic resistance 4. Clinical signs of congestion Exclusion Criteria: 1. Acute coronary syndrome 2. Systolic blood pressure \<85 mmHg 3. Use of renal replacement therapy or ultrafiltration in-hospital before study inclusion 4. Treatment with acetazolamide or metolazone during hospitalization prior to randomization

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '3-arm parallel group RCT', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'The study will employ a triple-blind design (Participants and relatives, investigators and clinicians, and data analysts and outcome adjudicators)', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 939, 'type': 'ESTIMATED'}}

Updated at

2023-12-18

1 organization

2 products

1 indication

Organization

Product

Indication

Product