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

Acute Heart Failure Clinical Trial

— P-Value-AHF  

Official title:

Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance (P-Value-AHF): A Multicentre, Randomized, Parallel-group, Open-label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05986773
• Other study ID #: P-Value-AHF
• Status: Recruiting
• Phase: Phase 4
• Start date: October 10, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Stadtspital Zürich
• Contact: Mattia Arrigo, PD, Dr. med.
• Phone: +41 44 416 30 03
• Email: mattia.arrigo[@]stadtspital.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 31, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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 first standard dose Furosemide i.v. (i.e., urine volume < 300 ml and urine sodium concentration < 70 mmol/L)

• Plasma N terminal-proBNP level at admission > 1000 ng/L

• Signed Informed Consent form

Exclusion Criteria:

• Previous use of intravenous diuretics during the index hospitalization (exception first standard dose Furosemide i.v.)

• 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.

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• 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).
• 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).
• 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).

Locations

Country	Name	City	State
Switzerland	Stadtspital Zürich	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
Stadtspital Zürich	Ospedale Regionale di Lugano

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Outcomes 1	Hypotension (SBP< 90 mmHg) with symptoms or requiring therapeutic intervention	0-24 hours after administration of the study-specific diuretic regimen
Other	Safety Outcomes 2	Increase in serum creatinine >50% from baseline	0-24 hours after administration of the study-specific diuretic regimen
Other	Safety Outcomes 3	New electrolyte disturbances (sodium < 130mmol/l or > 150mmol/l, potassium < 3.0mmol/l or > 5.5 mmol/l)	0-24 hours after administration of the study-specific diuretic regimen
Primary	Diuretic efficacy after 6h	urine- natrium concentration (mmol/L)	6 hours after administration of the study-specific diuretic regimen
Secondary	Diuretic efficacy after 2h	urine- natrium concentration (mmol/L)	2 hours after administration of the study-specific diuretic regimen
Secondary	Diuretic efficacy after 24h	urine- natrium concentration (mmol/L)	24 hours after administration of the study-specific diuretic regimen
Secondary	Change in clinical congestion	EVEREST congestion score	0 and 24 hours after administration of the study-specific diuretic regimen
Secondary	Change in dyspnea severity	numeric rating scale	0 and 24 hours after administration of the study-specific diuretic regimen.