Finding the best diuretic treatment for acute heart failure with fluid overload

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

This study is testing whether adding Metolazone or Acetazolamide to standard diuretic treatment can help adults with acute heart failure and fluid overload feel better and spend more days out of the hospital.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 939 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Copenhagen University Hospital, Hvidovre (Academic / other)
• Locations: 3 sites (Hvidovre, Capital Region of Denmark and 2 other locations)
• Trial ID: NCT06166654 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to identify the most effective treatment strategy for patients with acute heart failure (AHF) experiencing volume overload, particularly those resistant to standard loop-diuretics. It is a double-blinded, randomized, controlled, multicenter trial comparing the efficacy of loop-diuretics combined with either Metolazone or Acetazolamide against loop-diuretics alone. The study will assess the number of days alive and out-of-hospital by day 30 as the primary outcome, along with secondary outcomes such as clinical benefits and quality of life scores. Eligible participants include adults hospitalized with AHF and signs of congestion who are at risk of diuretic resistance.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years old hospitalized with acute heart failure and volume overload, showing signs of congestion and at risk of diuretic resistance.

Not a fit: Patients with acute coronary syndrome, low systolic blood pressure, or those who have previously received certain diuretic treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with acute heart failure and fluid overload, potentially improving their recovery and quality of life.

How similar studies have performed: Other studies have explored diuretic therapies for heart failure, but this specific combination approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Acute hospital admission with a clinical diagnosis of acute heart failure with volume overload.
3. Display risk of diuretic resistance, characterized by:

   1. Daily loop-diuretics administration for a minimum of 7 days before admission, or
   2. 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).
4. 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:

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 the index hospitalization prior to randomization
5. Known allergy to any of the used drugs
6. Severe hypokalemia (\<2.5 mmol/l) or severe hyponatremia (\<125 mmol/l)
7. Severe hepatic impairment or liver cirrhosis
8. Known pregnancy

Where this trial is running

Hvidovre, Capital Region of Denmark and 2 other locations

• Amager-Hvidovre Hospital — Hvidovre, Capital Region of Denmark, Denmark (Recruiting)
• Bispebjerg Hospital — Copenhagen, Denmark (Not_yet_recruiting)
• Herlev-Gentofte hospital — Copenhagen, Denmark (Recruiting)

Study contacts

• Principal investigator: Johannes Grand, MD, Phd, MPH — Amager-Hvidovre Hospital
• Study coordinator: Johannes Grand, MD, Phd, MPH

Conditions Acute Heart Failure; acute heart failure; decongestion; diuretic