Clinical trial NCT06092437: Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients
Official title: TAILOR-AHF: Randomized Trial Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure Acute
Keywords: Decongestion
Heart failure
Natriuresis
Urinary Sodium
Lead sponsor: Zuyderland Medisch Centrum
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Hierarchical composite of all-cause mortality, heart failure events and delta quality of life at 90 days follow-up.
timeFrame: 90 days after inclusion
Secondary outcomes:
measure: Delta NT-pro BNP
timeFrame: From admission to discharge and 90 days after hospitalisation
measure: Successful decongestion
timeFrame: Day 3 after inclusion
measure: Change in clinical congestion score
timeFrame: From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days),
measure: Quality of life (Kansas City Cardiomyopathy Questionnaire)
timeFrame: 90 days after inclusion
measure: Adverse (safety) events
timeFrame: 90 days after inclusion
measure: All-cause mortality and heart failure readmissions
timeFrame: 14 days after inclusion
measure: Chronic dialysis
timeFrame: 90 days after inclusion
measure: Days alive outside the hospital
timeFrame: 90 days after inclusion
measure: Time to first heart failure hospitalization and number of heart failure hospitalizations
timeFrame: 90 days after inclusion
measure: Number of outpatient visits
timeFrame: 90 days after inclusion
measure: Number of worsening heart failure events
timeFrame: 90 days after inclusion
measure: Delta weight
timeFrame: From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days)
Other outcomes:
Locations:
city: Heerlen
country: Netherlands
facility: Zuyderland MC
state: Limburg
Study officials:
References: