Optimal Diuretic Therapies for Acute Heart Failure with Volume Overload

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Sep 2024 → ongoing

Decision date (initial)

2024-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Danish Regions Fund For health Care Research · Danish Heart Foundation

External identifiers

EU CT number

2024-510633-17-00

ClinicalTrials.gov

NCT06166654

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The main objective is to determine the most effective diuretic treatment strategy for patients with acute decompensated heart failure who have volume overload and are at risk of diuretic resistance.

Conditions and MedDRA coding

acute heart failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Aged 18 years or older. 2. Admitted acutely with a clinical diagnosis of acute heart failure. 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

1. 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 defined as an INR > 1.5 (not due to anticoagulant therapy) and/or a Child-Pugh score ≥ B7 8. Known pregnancy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Days alive and outside hospital until day 30

Secondary endpoints 1

1. 1. Clinical benefit at 30 days, consisting of a composite of 1. all-cause death, 2. Readmission 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. 2. Days alive and outside hospital until day 90 3. Days of admittance in the primary admission

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Kettegaard Alle 30

City

Hvidovre

Postcode

2650

Country

Denmark

Scientific contact point

Organisation

Hvidovre Hospital

Contact name

Johannes Grand

Public contact point

Organisation

Hvidovre Hospital

Contact name

Johannes Grand

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications