Investigating a Tailored Diuretic Algorithm in Acute Heart Failure Patients
- Conditions
- Heart Failure Acute
- Interventions
- Other: Urine sodium guided diuretic algorithmOther: Usual care
- Registration Number
- NCT06092437
- Lead Sponsor
- Zuyderland Medisch Centrum
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 466
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tailored, Urine sodium guided, intensified diuretic strategy Urine sodium guided diuretic algorithm - Usual care Usual care -
- Primary Outcome Measures
Name Time Method Hierarchical composite of all-cause mortality, heart failure events and delta quality of life at 90 days follow-up. 90 days after inclusion 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
- Secondary Outcome Measures
Name Time Method Quality of life (Kansas City Cardiomyopathy Questionnaire) 90 days after inclusion Quality of life assessed using the Kansas City Cardiomyopathy Questionnaire
Delta weight From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days) Delta weight (in kilograms) from admission to discharge
All-cause mortality and heart failure readmissions 14 days after inclusion All-cause mortality and heart failure readmissions at 14 days follow up
Days alive outside the hospital 90 days after inclusion Days alive outside the hospital at 90-days follow up
Number of outpatient visits 90 days after inclusion Number of outpatient visits in the first 90 days
Delta NT-pro BNP From admission to discharge and 90 days after hospitalisation Delta NT-proBNP from admission to discharge and 90-days follow up
Successful decongestion Day 3 after inclusion Number of participants with successful decongestion (defined as a clinical congestion score of 2 or less and NYHA I-II)
Time to first heart failure hospitalization and number of heart failure hospitalizations 90 days after inclusion Time to first heart failure hospitalization and number of heart failure hospitalizations
Change in clinical congestion score From date of randomization until date of hospital discharge (regarding initial hospitalisation at time of randomisation, assessed up to 90 days), Change in clinical congestion score from admission to discharge
Adverse (safety) events 90 days after inclusion 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
Chronic dialysis 90 days after inclusion Occurence of the need for chronic dialysis at 90-days follow up
Number of worsening heart failure events 90 days after inclusion 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
Trial Locations
- Locations (1)
Zuyderland MC
🇳🇱Heerlen, Limburg, Netherlands