Acute Heart Failure, Diuretic Resistance
Conditions
Keywords
Diuretic therapy
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).
Interventions
DRUGFurosemide
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).
DRUGMetolazone
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).
DRUGAcetazolamide
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).
Sponsors
Ospedale Regionale di Lugano
Stadtspital Zürich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diuretic efficacy after 6h | 6 hours after administration of the study-specific diuretic regimen | urine- natrium concentration (mmol/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diuretic efficacy after 24h | 24 hours after administration of the study-specific diuretic regimen | urine- natrium concentration (mmol/L) |
| Diuretic efficacy after 2h | 2 hours after administration of the study-specific diuretic regimen | urine- natrium concentration (mmol/L) |
| Change in clinical congestion | 0 and 24 hours after administration of the study-specific diuretic regimen | EVEREST congestion score |
| Change in dyspnea severity | 0 and 24 hours after administration of the study-specific diuretic regimen. | numeric rating scale |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcomes 3 | 0-24 hours after administration of the study-specific diuretic regimen | New electrolyte disturbances (sodium \< 130mmol/l or \> 150mmol/l, potassium \< 3.0mmol/l or \> 5.5 mmol/l) |
| Safety Outcomes 2 | 0-24 hours after administration of the study-specific diuretic regimen | Increase in serum creatinine \>50% from baseline |
| Safety Outcomes 1 | 0-24 hours after administration of the study-specific diuretic regimen | Hypotension (SBP\< 90 mmHg) with symptoms or requiring therapeutic intervention |
Countries
Switzerland
Outcome results
None listed