Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients

NCT ID: NCT06092437

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 466 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-27
• Study Completion Date: 2026-08-27

Brief Summary

Acutely decompensated heart failure (ADHF) is highly prevalent and has a high (financial) burden on the health care system. Treatment often consists of the administration of IV decongestive agents. Adequate dosing is difficult due to varying diuretic resistance and inadequate parameters to evaluate the response. Urine sodium is a promising biomarker to evaluate the diuretic response. It is hypothesized that a tailored, urine sodium guided diuretic algorithm will result in faster and more complete decongestion and therefore lead to better survival (in terms of mortality and heart failure events) while being non-inferior in terms of safety (mainly regression of kidney function).

Detailed Description

Rationale: Acutely decompensated heart failure is a highly prevalent diagnosis with a high burden on resources and a high risk of mortality and re-hospitalization. The prescription of diuretics to relieve congestion has been the cornerstone of treatment for years, but evidence about diuretic response and adequate dosing is still lacking. Inadequate diuretic response (and insufficient decongestion) has a negative influence on outcome but is often not timely addressed. Urinary sodium (Ur-Na) is a promising biomarker in the prediction of diuretic response to the prescribed dose. It is hypothesized that an Ur-Na based, intensified algorithm can help tailor diuretics in an individual way, but sufficient evidence to support its implementation is lacking.

Objective: Investigate if a tailored diuretic algorithm based on Ur-Na has a positive effect on a primary endpoint of reduction in a combined endpoint of death, heart failure events and change in the Kansas City questionnaire total symptom score (KCCQ-TSS) versus standard clinical care in patients hospitalized with AHF, without imposing safety concerns (e.g. worsening renal function).

Study design: Prospective, Single-Blinded, Randomized, Blinded-endpoint trial

Study population: Patients admitted with acutely decompensated heart failure (diagnosed according to the 2021 ESC (European Society of Cardiology) guidelines) who are 18 year or older.

Intervention: Arm I: Tailored, Ur-Na based, intensified diuretic strategy; Arm II: Usual care

Main study parameters/endpoints: Hierarchical composite endpoint of all-cause death, heart failure events and a 4-point or greater difference in Kansas City questionnaire total symptom score (KCCQ-TSS); assessed using a win-ratio approach.

Conditions

Heart Failure Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tailored, Urine sodium guided, intensified diuretic strategy

Group Type: EXPERIMENTAL

Urine sodium guided diuretic algorithm

Intervention Type: OTHER

Loop diuretics are administered intravenously as soon as possible after diagnosis of ADHF and continued 3dd until recompensation. Spot urine sodium is measured 2 hours after administration of the first in-hospital IV diuretic dose and repeated until the target of 100mmol/L is reached in the first 72 hours of admission (after which, UrNa will be measured once daily). When target is not met, the next dosage of loop diuretic is doubled (max 3dd 250mg furosemide) and thereafter, other diuretics (thiazide, MRA) are added. Acetazolamide in the first 72 hours is advised as background therapy in both treatment arms.

Usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Treatment with IV loop diuretics left to the discretion of the treating physician. Acetazolamide in the first 72 hours is advised as background therapy in both treatment arms.

Interventions

Urine sodium guided diuretic algorithm

Loop diuretics are administered intravenously as soon as possible after diagnosis of ADHF and continued 3dd until recompensation. Spot urine sodium is measured 2 hours after administration of the first in-hospital IV diuretic dose and repeated until the target of 100mmol/L is reached in the first 72 hours of admission (after which, UrNa will be measured once daily). When target is not met, the next dosage of loop diuretic is doubled (max 3dd 250mg furosemide) and thereafter, other diuretics (thiazide, MRA) are added. Acetazolamide in the first 72 hours is advised as background therapy in both treatment arms.

Intervention Type: OTHER

Usual care

Treatment with IV loop diuretics left to the discretion of the treating physician. Acetazolamide in the first 72 hours is advised as background therapy in both treatment arms.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age > 18 years;
• HF (HFrEF, HFmrEF or HFpEF) diagnosed according to the 2021 HF Guidelines of the European Society of Cardiology [5];
• Presentation with AHF meaning at least one symptom (dyspnea, orthopnea, or edema) and one sign (rales, peripheral edema, ascites, or pulmonary vascular congestion on chest radiography) of AHF;
• An elevated NT-proBNP >300pg/ml;
• Requiring the need for iv diuretics.

Exclusion Criteria

• Terminal renal insufficiency defined as: dialysis patients or eGFR (estimated glomerular filtration rate) < 10 mL/min/1.73 m2;
• Patients included in other investigational studies regarding heart failure.
• Presentation with cardiogenic shock or respiratory insufficiency or another reason requiring admission to the intensive care unit upon admission (IC transfer later in the hospitalization is not an exclusion).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zuyderland Medisch Centrum

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Zuyderland MC

Heerlen, Limburg, Netherlands

Site Status: RECRUITING

Amphia ziekenhuis

Breda, North Brabant, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Sandra van Wijk, MD, PhD

Role: CONTACT

s.vanwijk@zuyderland.nl

088 - 459 9701

Mick Hoen, MD

Role: CONTACT

m.hoen@zuyderland.nl

088 - 459 9701

Facility Contacts

Sandra van Wijk, MD, PhD

Role: primary

088 - 459 9701

Mick Hoen, MD

Role: backup

088 - 459 9701

Ijsbrand dr. Klip, MD, PhD

Role: primary

RDCardio@amphia.nl

+31765953018

Other Identifiers

Z2021110

Identifier Type: -

Identifier Source: org_study_id