Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload
Recruiting · NCT06166654 · Interventional (participants receive a specific treatment) · Lead sponsor: Johannes Grand
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Inclusion criteria
- Age ≥ 18 years
- Acute hospital admission with a clinical diagnosis of acute heart failure with volume overload.
- Display risk of diuretic resistance, characterized by:
- 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).
- Clinical signs of congestion, indicated by one or more of the following: pitting peripheral edema, ascites, elevated jugular venous pressure, or radiological/ultrasonic evidence of pulmonary congestion.
Exclusion criteria
- 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
- Known allergy to any of the used drugs
- Severe hypokalemia (\<2.5 mmol/l) or severe hyponatremia (\<125 mmol/l)
- Severe hepatic impairment or liver cirrhosis
- Known pregnancy
Where it is running
5 locations listed.
- Aarhus university Hospital - Aarhus, Denmark
- Bispebjerg Hospital - Copenhagen, Denmark
- Herlev-Gentofte hospital - Copenhagen, Denmark
- Zealand University Hospital - Roskilde, Denmark
- Amager-Hvidovre Hospital - Hvidovre, Capital Region of Denmark, Denmark