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

NCT ID: NCT05986773

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-10
• Study Completion Date: 2024-12-31

Brief Summary

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

Detailed Description

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).

Conditions

Acute Heart Failure; Diuretic Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

group FF

Group FF will receive a doubled dose Furosemide i.v.

The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.

Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection.

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

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).

group FM

Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.

The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.

Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally.

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

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).

Metolazone

Intervention Type: DRUG

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).

group FA

Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.

The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.

Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion.

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

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).

Acetazolamide

Intervention Type: DRUG

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).

Interventions

Furosemide

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).

Intervention Type: DRUG

Metolazone

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).

Intervention Type: DRUG

Acetazolamide

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).

Intervention Type: DRUG

Other Intervention Names

Furosemide, doubled dose; Furosemide + Metolazone; Furosemide + Acetazolamide

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ospedale Regionale di Lugano

OTHER

Sponsor Role: collaborator

Stadtspital Zürich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mattia Arrigo, PD, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland

Locations

Stadtspital Zürich

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

Other Identifiers

P-Value-AHF

Identifier Type: -

Identifier Source: org_study_id