Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST)

Vrije Universiteit Brussel

Status and phase: Completed; Phase 4

Conditions: Diuretics Drug Reactions; Acute Heart Failure

Treatments: Drug: Oral chlorthalidone OD; Drug: Oral potassium supplements; Other: Usual AHF care; Drug: Intravenous acetazolamide 500 mg OD; Diagnostic Test: UNa measurement after intravenous loop diuretic bolus; Other: Intravenous hypertonic saline; Drug: Intravenous canrenoate 200 mg OD; Other: Switch to oral diuretic therapy; Drug: Intravenous bumetanide TID; Other: Maintenance infusion

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05411991

EC-2021-236

2021-005426-18 (EudraCT Number)

Details and patient eligibility

About

This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.

Full description

Key interventions are:

• Assessment of UNa in spot urine samples after every bolus administration of loop diuretics with continuation of intravenous diuretics until resolution of clinical signs of fluid overload AND UNa <80 mmol/L
• Dosing of loop diuretic bolus according to estimated glomerular filtration rate (eGFR)
• Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia (>145 mmol/L) or metabolic acidosis (bicarbonate <22 mmol/L)
• Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia (>145 mmol/L)
• Switch to full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa <80 mmol/L and persistent clinical signs of fluid overload
• Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during diuretic therapy with intravenous diuretics

Enrollment: 107 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• At least 18 y/o and able to provide informed consent

• Hospital admission (anticipated stay >24 h after randomisation) with diagnosis of acute heart failure according to the treating physician

• At least one of the following three signs of volume overload:

  1. bilateral oedema 2+, indicating clear pitting
  2. ascites that is amenable for drainage, confirmed by echography (no obligation to perform abdominal echocardiography, but necessary when presence of ascites is used as an entry criterion for the study)
  3. uni- or bilateral pleural effusions that are amenable for drainage, confirmed by chest X-ray or lung ultrasound (no obligation to perform chest X-ray, but necessary when presence of pleural effusions is used as an entry criterion for the study)

• Plasma NTproBNP level >1,000 ng/L

Exclusion criteria

• No possibility to collect reliable urine spot samples after diuretic administration
• Administration of any diuretic within 6 h before randomisation, except for a mineralocorticoid receptor antagonist or sodium glucose co-transporter-2 inhibitor as part of the patient's maintenance treatment for heart failure. Patients can still be included after withholding these diuretics for 6 h, after which randomisation can be performed if they qualify all other criteria.
• Severe kidney dysfunction, defined as an eGFR <15 mL/min/1.73m² calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and/or previous, current, or planned future renal replacement therapy
• Systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or need for inotropes/vasopressor therapy at randomisation
• Any acute coronary syndrome within 30 days prior to enrolment, defined as typical chest pain with a troponin rise above the 99th percentile of normal and/or electrocardiographic changes suggestive of cardiac ischemia
• History of heart or kidney transplantation
• History of mechanical circulatory support
• Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute mechanical cause of acute heart failure (e.g., papillary muscular rupture), acute myocarditis, or constrictive pericarditis according to the treating physician
• Pregnant or breastfeeding woman
• Concomitant participation in another interventional study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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107 participants in 2 patient groups

Intervention arm

Experimental group

Description:

Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics

Treatment:

Other: Maintenance infusion

Drug: Intravenous bumetanide TID

Other: Switch to oral diuretic therapy

Drug: Intravenous canrenoate 200 mg OD

Other: Intravenous hypertonic saline

Diagnostic Test: UNa measurement after intravenous loop diuretic bolus

Drug: Intravenous acetazolamide 500 mg OD

Drug: Oral potassium supplements

Drug: Oral chlorthalidone OD

Control arm

Active Comparator group

Description:

Usual care for AHF. It is recommended to administer an intravenous loop diuretic dose at least BID (or through continuous infusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered in an optimal volume status as is recommended by current guidelines. Urine electrolyte assessment in the control arm is not allowed as it is a key component of the studied intervention.

Treatment:

Other: Usual AHF care