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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05986773
Other study ID # P-Value-AHF
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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.
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