Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Другое 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 (thi
• Другое 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.

Первичные конечные точки

• Hierarchical composite of all-cause mortality, heart failure events and delta quality of life at 90 days follow-up. [Срок оценки: 90 days after inclusion]

Вторичные конечные точки (12)

• Delta NT-pro BNP [Срок оценки: From admission to discharge and 90 days after hospitalisation]
• Successful decongestion [Срок оценки: Day 3 after inclusion]
• Change in clinical congestion score [Срок оценки: 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) [Срок оценки: 90 days after inclusion]
• Adverse (safety) events [Срок оценки: 90 days after inclusion]
• All-cause mortality and heart failure readmissions [Срок оценки: 14 days after inclusion]
• All-cause mortality and heart failure readmissions [Срок оценки: 6 months after inclusion]
• Chronic dialysis [Срок оценки: 90 days after inclusion]
• Days alive outside the hospital [Срок оценки: 90 days after inclusion]
• Time to first heart failure hospitalization and number of heart failure hospitalizations [Срок оценки: 90 days after inclusion]
• Number of outpatient visits [Срок оценки: 90 days after inclusion]
• Number of worsening heart failure events [Срок оценки: 90 days after inclusion]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Нидерланды · 2 центра

• Zuyderland MC — Heerlen
• Amphia ziekenhuis — Breda

Идентификаторы

NCT: NCT06092437 · Z2021110

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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