Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients

Heart Failure Acute Clinical Trial

— TAILOR-AHF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06092437
• Other study ID #: Z2021110
• Status: Recruiting
• Phase: N/A
• Start date: February 27, 2023
• Est. completion date: February 27, 2026

Study information

• Verified date: August 2023
• Source: Zuyderland Medisch Centrum
• Contact: Sandra van Wijk, MD, PhD
• Phone: 088 - 459 9701
• Email: s.vanwijk[@]zuyderland.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 466
• Est. completion date: February 27, 2026
• Est. primary completion date: June 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure Acute

Intervention

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.
• 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.

Locations

Country	Name	City	State
Netherlands	Zuyderland MC	Heerlen	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Zuyderland Medisch Centrum

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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),
Secondary	Quality of life (Kansas City Cardiomyopathy Questionnaire)	Quality of life assessed using the Kansas City Cardiomyopathy Questionnaire	90 days after inclusion
Secondary	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
Secondary	All-cause mortality and heart failure readmissions	All-cause mortality and heart failure readmissions at 14 days follow up	14 days after inclusion
Secondary	Chronic dialysis	Occurence of the need for chronic dialysis at 90-days follow up	90 days after inclusion
Secondary	Days alive outside the hospital	Days alive outside the hospital at 90-days follow up	90 days after inclusion
Secondary	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
Secondary	Number of outpatient visits	Number of outpatient visits in the first 90 days	90 days after inclusion
Secondary	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
Secondary	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)