Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients (TAILOR-AHF)

TAILOR-AHF: Randomized Trial Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients

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).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure Acute
• Intervention / Treatment: Other: Urine sodium guided diuretic algorithm; Other: Usual care

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.

• Study Type: Interventional
• Enrollment (Estimated): 556
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandra van Wijk, MD, PhD; Phone Number: 088 - 459 9701; Email: s.vanwijk@zuyderland.nl
• Study Contact Backup: Name: Mick Hoen, MD; Phone Number: 088 - 459 9701; Email: m.hoen@zuyderland.nl

Study Locations

• Netherlands
  • Limburg
    • Heerlen, Limburg, Netherlands, 6419 PC
      • Recruiting
      • Zuyderland MC
      • Contact: Sandra van Wijk, MD, PhD; Phone Number: 088 - 459 9701
      • Contact: Mick Hoen, MD; Phone Number: 088 - 459 9701
  • North Brabant
    • Breda, North Brabant, Netherlands, 4818 CK
      • Recruiting
      • Amphia Ziekenhuis
      • Contact: Ijsbrand dr. Klip, MD, PhD; Phone Number: +31765953018; Email: RDCardio@amphia.nl
      • Principal Investigator: Ijsbrand Dr. Klip, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care	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.
Experimental: Tailored, Urine sodium guided, intensified diuretic strategy	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite of all-cause mortality, heart failure events and delta quality of life at 90 days follow-up.	The primary endpoint is a hierarchical composite calculated using a win-ratio approach of: i) Mortality (all-cause) at 90 days after hospitalization; ii) Heart failure events at 90 days after hospitalization (1. a >2 times increase in oral loop diuretic dose, 2. the need for iv administration of loop diuretics, 3. an emergency department visit or hospitalization for HF), wherein a single event or hospitalization will be sufficient to reach the combined endpoint; iii) Delta in quality of life measured using the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) from baseline to 90 days after hospitalization	90 days after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta NT-pro BNP	Delta NT-proBNP from admission to discharge and 90-days follow up	From admission to discharge and 90 days after hospitalisation
Successful decongestion	Number of participants with successful decongestion (defined as a clinical congestion score of 2 or less and NYHA I-II)	Day 3 after inclusion
Change in clinical congestion score	Change in clinical congestion score from admission to discharge	From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days),
Quality of life (Kansas City Cardiomyopathy Questionnaire)	Quality of life assessed using the Kansas City Cardiomyopathy Questionnaire	90 days after inclusion
Adverse (safety) events	All-cause readmissions at 90-days, all-cause and cardiovascular mortality at 90-days, (symptomatic) hypotension, hypokalemia, urinary tract infection, phlebitis, atrial fibrillation, fall/trauma and decompensated HF	90 days after inclusion
All-cause mortality and heart failure readmissions	All-cause mortality and heart failure readmissions at 14 days follow up	14 days after inclusion
Chronic dialysis	Occurence of the need for chronic dialysis at 90-days follow up	90 days after inclusion
Days alive outside the hospital	Days alive outside the hospital at 90-days follow up	90 days after inclusion
Time to first heart failure hospitalization and number of heart failure hospitalizations	Time to first heart failure hospitalization and number of heart failure hospitalizations	90 days after inclusion
Number of outpatient visits	Number of outpatient visits in the first 90 days	90 days after inclusion
Number of worsening heart failure events	Number of worsening heart failure events at 90 days: i) a >2 times increase in oral loop diuretic dose, ii) the need for iv administration of loop diuretics, iii) an emergency department visit or hospitalization for HF	90 days after inclusion
Delta weight	Delta weight (in kilograms) from admission to discharge	From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days)
All-cause mortality and heart failure readmissions	All-cause mortality and heart failure readmissions at 6 months follow up	6 months after inclusion
Hospital length of stay	Number of days from hospitalization untill discharge or end of clinical treatment (not including days waiting for post-hospital care)	Number of days from hospitalization untill end of clinical treatment (not including days waiting for post-hospital care) or hospital discharge, whichever came first, assessed up to 90 days after randomization.
Worsening renal function	Delta creatinine from baseline until discharge and 90 days follow-up	Baseline until 90 days follow-up

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Estimated): June 27, 2026
• Study Completion (Estimated): August 27, 2026

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Heart failure; Natriuresis; Decongestion; Urinary Sodium
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Natriuretic Agents; Diuretics
• Other Study ID Numbers: Z2021110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No