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

NCT05986773 | Terminated Phase 4 DMC

• 1 other identifier: P-Value-AHF
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Heart Failure; Diuretic Resistance

Keywords

Diuretic therapy

Outcome Measures

Primary Outcomes (1)

• Diuretic efficacy after 6h

  urine- natrium concentration (mmol/L)

  6 hours after administration of the study-specific diuretic regimen

Secondary Outcomes (4)

• Diuretic efficacy after 2h

  2 hours after administration of the study-specific diuretic regimen

• Diuretic efficacy after 24h

  24 hours after administration of the study-specific diuretic regimen

• Change in clinical congestion

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

• Change in dyspnea severity

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

Other Outcomes (3)

• Safety Outcomes 1

  0-24 hours after administration of the study-specific diuretic regimen

• Safety Outcomes 2

  0-24 hours after administration of the study-specific diuretic regimen

• Safety Outcomes 3

  0-24 hours after administration of the study-specific diuretic regimen

Study Arms (3)

group FF

ACTIVE COMPARATOR

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.

Drug: Furosemide

group FM

ACTIVE COMPARATOR

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.

Drug: Furosemide; Drug: Metolazone

group FA

ACTIVE COMPARATOR

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.

Drug: Furosemide; Drug: Acetazolamide

Interventions

Furosemide 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).

Also known as: Furosemide, doubled dose

group FA; group FF; group FM

Metolazone 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).

Also known as: Furosemide + Metolazone

group FM

Acetazolamide 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).

Also known as: Furosemide + Acetazolamide

group FA

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Maintenance treatment with Acetazolamide or Metolazone
• 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 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.

Sponsors & Collaborators

• Stadtspital Zürich: lead
• Ospedale Regionale di Lugano: collaborator

Study Sites (1)

Stadtspital Zürich

Zurich, Canton of Zurich, 8063, Switzerland

Location

MeSH Terms

Interventions

Furosemide; Metolazone; Acetazolamide

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiadiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Mattia Arrigo, PD, Dr. med.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: August 14, 2023
• Study Start: October 10, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)