Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance

Phase 4TerminatedNCT05986773

Stadtspital Zürich13 enrolled

Overview

The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure and diuretic resistance. The main aims are * to compare the diuretic efficacy of three therapeutic strategies in patients with acute heart failure and diuretic resistance. * to assess the improvement in clinical congestion and to compare the symptom-relief among the different treatment regimens

The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure (AHF) and diuretic resistance (DR). Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens. Two to five hours after the initial standard dose Furosemide i.v, * the first group will receive a doubled dose Furosemide (group FF) * the second group will receive a combination of standard dose Furosemide and Metolazone (group FM) * the third group will receive a combination of standard dose Furosemide and Acetazolamide (group FA) Objectives * The primary objective is to compare the diuretic efficacy (measured as natriuresis and urine volume) of three therapeutic strategies in patients with acute heart failure and diuretic resistance. * The secondary objective is to assess the improvement in clinical congestion (EVEREST congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS)) among the different treatment regimens (FF vs. FM vs. FA).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Heart Failure Diuretic Resistance

Interventions

FurosemideDRUG

Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).

MetolazoneDRUG

Acetazolamide

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Elective or emergency hospital admission with clinical diagnosis of acute heart failure * One or more clinical signs of volume overload (i.e., peripheral edema, pleural effusion, jugular venous distension) * Low diuretic efficacy in the first 2 hours after the standard screening dose Furosemide i.v. (i.e., urine volume \< 300 ml and urine sodium concentration \< 70 mmol/L) * Plasma N terminal-proBNP level at enrolment \> 1000 ng/L * Signed Informed Consent form Exclusion Criteria: * Maintenance treatment with Acetazolamide or Metolazone * Use of any non-protocol defined diuretic agent that cannot be stopped upon study inclusion except for sodium-glucose co-transporter-2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin) and mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone) * Systolic blood pressure \< 90 mmHg * Expected use of intravenous vasopressors (e.g., noradrenaline, adrenaline), inotropes (e.g., dobutamine, milrinone, levosimendan) at any time point during the study * Severe chronic kidney disease (estimated glomerular filtration rate \< 15 ml/min/1.73 m2) or use of renal replacement therapy at any time before study inclusion * Severe liver dysfunction or cirrhosis at risk of hepatic encephalopathy * Severe electrolyte disturbances or metabolic acidosis requiring specific intravenous treatment * Concurrent diagnosis of acute coronary syndrome requiring urgent revascularization * History of cardiac transplantation or ventricular assist device * Allergy, intolerance or other contraindication against one of the study drugs * Pregnancy or breastfeeding * Age below 18 years.

Locations (1)

Stadtspital Zürich

Zurich, Canton of Zurich, Switzerland

Outcomes

Primary Outcomes

Diuretic efficacy after 6h

urine- natrium concentration (mmol/L)

Time frame: 6 hours after administration of the study-specific diuretic regimen

Secondary Outcomes

Diuretic efficacy after 2h

urine- natrium concentration (mmol/L)

Time frame: 2 hours after administration of the study-specific diuretic regimen

Diuretic efficacy after 24h

urine- natrium concentration (mmol/L)

Time frame: 24 hours after administration of the study-specific diuretic regimen

Change in clinical congestion

EVEREST congestion score

Time frame: 0 and 24 hours after administration of the study-specific diuretic regimen

Change in dyspnea severity

numeric rating scale

Time frame: 0 and 24 hours after administration of the study-specific diuretic regimen.

Data from ClinicalTrials.gov

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