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Recruiting Phase 4 NCT06166654

NCT06166654 Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload

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Clinical Trial Summary
NCT ID NCT06166654
Status Recruiting
Phase Phase 4
Sponsor Johannes Grand
Condition Acute Heart Failure
Study Type INTERVENTIONAL
Enrollment 939 participants
Start Date 2024-09-05
Primary Completion 2027-09-30

Eligibility & Interventions

Sex All sexes
Min Age 18 Years
Max Age N/A
Study Type INTERVENTIONAL
Interventions
AcetazolamideMetolazone 2.5 MGDouble-placebo

Eligibility Fast-Check

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 4 studies follow an already-approved treatment in real-world conditions to monitor long-term safety and effectiveness.

This trial targets 939 participants in total. It began in 2024-09-05 with a primary completion date of 2027-09-30.

⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.

Brief Summary

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

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

Contact & Investigator

Central Contact

Johannes Grand, MD, Phd, MPH

✉ johannes.grand@regionh.dk

📞 +4535452121

Principal Investigator

Johannes Grand, MD, Phd, MPH

PRINCIPAL INVESTIGATOR

Amager-Hvidovre Hospital

Frequently Asked Questions

Who can join the NCT06166654 clinical trial?

This trial is open to participants of all sexes, aged 18 Years or older, studying Acute Heart Failure. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.

What phase is the NCT06166654 trial and what does that mean for participants?

Phase 4 studies are conducted after a treatment has been approved. They monitor long-term safety and real-world effectiveness in a broader patient population.

Is NCT06166654 currently recruiting?

Yes, NCT06166654 is actively recruiting participants. Contact the research team at johannes.grand@regionh.dk for enrollment information.

Where is the NCT06166654 trial being conducted?

This trial is being conducted at Hvidovre, Denmark, Copenhagen, Denmark, Copenhagen, Denmark.

Who is sponsoring the NCT06166654 clinical trial?

NCT06166654 is sponsored by Johannes Grand. The principal investigator is Johannes Grand, MD, Phd, MPH at Amager-Hvidovre Hospital. The trial plans to enroll 939 participants.

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ClinicalMetric — Independent clinical trial intelligence platform. Not affiliated with NIH, ClinicalTrials.gov, the U.S. FDA, or any pharmaceutical company, hospital, or clinical research organization. Trial data is sourced from ClinicalTrials.gov for informational purposes only and does not constitute medical advice. Do not make any treatment, enrollment, or health decisions based solely on information found here — always consult a qualified healthcare professional. Full Disclaimer  ·  Last Reviewed: April 2026  ·  Data Methodology