Protocolised Natriuresis-Guided Decongestion at Different Diuretic Intensities in Acute Heart Failure

Universiti Teknologi Mara109 enrolled

Overview

The goal of this clinical trial is to learn how different doses of a water-removing medicine (diuretic) work in adults admitted to hospital with acute heart failure. It will also assess the safety of these treatment approaches. The main questions this study aims to answer are: Does starting with a higher or lower dose of diuretic affect how much sodium and urine the body removes during the first 24 hours? Are there differences in side effects or short-term health outcomes between the treatment approaches? Researchers will compare two treatment approaches that use urine sodium and urine output to guide diuretic treatment with standard care. Participants will receive intravenous diuretic treatment and have their urine sodium, urine output, symptoms, blood tests, and clinical outcomes assessed.

DESTINaTE-AHF evaluated whether the intensity of upfront intravenous loop diuretic therapy influences early decongestive response when treatment is subsequently guided by objective measures of diuretic response. Urinary sodium concentration and urine output were assessed early after treatment and incorporated into predefined treatment algorithms to identify inadequate response and guide subsequent diuretic therapy during the first 24 hours. Two natriuresis-guided strategies using different upfront diuretic intensities were evaluated against usual clinician-directed care. This design allowed assessment of whether the initial intensity of loop diuretic therapy influences subsequent natriuretic and diuretic response within a protocolised response-guided approach.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

109

Conditions

Interventions

Furosemide - HIGH-dose Natriuresis-Guided StrategyDRUG

Intravenous furosemide was administered according to a predefined HIGH-dose natriuresis-guided protocol during the first 24 hours. For participants not receiving chronic loop diuretic therapy, the protocol-defined 24-hour dose was 80 mg. For chronic loop diuretic users, the protocol-defined 24-hour dose was calculated as 2.5 times their total home oral daily furosemide-equivalent dose and administered intravenously in divided doses. Urinary sodium at 2 and 6 hours and urine output at 6 hours were used to guide subsequent dosing according to predefined response criteria.

Furosemide - LOW-dose Natriuresis-Guided StrategyDRUG

Intravenous furosemide was administered according to a predefined LOW-dose natriuresis-guided protocol during the first 24 hours. For participants not receiving chronic loop diuretic therapy, the protocol-defined 24-hour dose was 60 mg. For chronic loop diuretic users, the protocol-defined 24-hour dose was calculated as 1.5 times their total home oral daily furosemide-equivalent dose and administered intravenously in divided doses. Urinary sodium at 2 and 6 hours and urine output at 6 hours were used to guide subsequent dosing according to predefined response criteria.

Loop Diuretic - Standard of CareDRUG

Intravenous loop diuretic therapy was administered according to the treating clinician's usual practice. The dose and subsequent adjustment of loop diuretic therapy were determined by the treating clinical team without a protocol-mandated dosing or escalation strategy. Urinary sodium and urine output were assessed at the same study time points as in the natriuresis-guided groups, but no protocol-directed treatment adjustment was mandated based on these measurements.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 years or older * Malaysian nationality * Hospitalised with acute heart failure, either de novo acute heart failure or acute decompensated chronic heart failure * Clinical evidence of congestion requiring intravenous loop diuretic therapy, with at least one of the following: peripheral oedema, orthopnoea, paroxysmal nocturnal dyspnoea, pulmonary crepitations, elevated jugular venous pressure, ascites, or congestive hepatomegaly * Able to provide informed consent Exclusion Criteria: * End-stage renal disease requiring chronic dialysis * Requirement or anticipated requirement for invasive mechanical ventilation * Requirement or anticipated requirement for inotropic or vasopressor support * Requirement or anticipated requirement for renal replacement therapy * Cardiogenic shock or systolic blood pressure below 100 mmHg * Pregnancy or breastfeeding * Known hypersensitivity to furosemide

Outcomes

Primary Outcomes

24-Hour Urinary Sodium Excretion

Total urinary sodium excretion during the first 24 hours after randomisation, calculated from the 24-hour urine collection and expressed in mmol.

Time frame: From randomisation to 24 hours

24-Hour Urine Volume

Total urine volume collected during the first 24 hours after randomisation, expressed in litres.

Time frame: From randomisation to 24 hours

Change From Baseline in Breathlessness Likert Score at 24 Hours

Change in participant-reported breathlessness from baseline to 24 hours, assessed using a 5-point Likert scale. Higher scores indicate greater improvement in breathlessness.

Time frame: Baseline and 24 hours after randomisation

Secondary Outcomes

Length of Stay

Duration of the index hospitalisation, calculated from the first day of hospital admission to discharge and expressed in days.

Time frame: From the date of hospital admission until the date of hospital discharge, assessed up to 30 days.

Worsening Renal Function at Discharge

Worsening renal function was defined as a doubling of serum creatinine or a greater than 50% reduction in estimated glomerular filtration rate (eGFR) at hospital discharge compared with baseline.

Time frame: From baseline to hospital discharge, assessed up to 30 days.

30-Day Unplanned Heart Failure Rehospitalisation

Number of participants with at least one unplanned hospital readmission for heart failure within 30 days after discharge from the index hospitalisation.

Time frame: From hospital discharge to 30 days after discharge

All-Cause Mortality Through 30 Days After Hospital Discharge

Number of participants who died from any cause from randomisation through 30 days after hospital discharge, including deaths occurring during the index hospitalisation.

Time frame: From randomisation to 30 days after hospital discharge