Clinical trial NCT05986773: Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Heart Failure
Diuretic Resistance
Keywords: Diuretic therapy
Lead sponsor: Stadtspital Zürich
Sponsor class: OTHER
Collaborators: name: Ospedale Regionale di Lugano
First posted: 2023-08-14
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Diuretic efficacy after 6h
timeFrame: 6 hours after administration of the study-specific diuretic regimen
Secondary outcomes:
measure: Diuretic efficacy after 2h
timeFrame: 2 hours after administration of the study-specific diuretic regimen
measure: Diuretic efficacy after 24h
timeFrame: 24 hours after administration of the study-specific diuretic regimen
measure: Change in clinical congestion
timeFrame: 0 and 24 hours after administration of the study-specific diuretic regimen
measure: Change in dyspnea severity
timeFrame: 0 and 24 hours after administration of the study-specific diuretic regimen.
Other outcomes:
measure: Safety Outcomes 1
timeFrame: 0-24 hours after administration of the study-specific diuretic regimen
measure: Safety Outcomes 2
timeFrame: 0-24 hours after administration of the study-specific diuretic regimen
measure: Safety Outcomes 3
timeFrame: 0-24 hours after administration of the study-specific diuretic regimen
Locations:
city: Zürich
country: Switzerland
facility: Stadtspital Zürich
Study officials:
affiliation: City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
name: Mattia Arrigo, PD, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: