P-Value-AHF: Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: group FF 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
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).
Other Names:
|
| Active Comparator: group FM 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
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).
Other Names:
Drug: 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).
Other Names:
|
| Active Comparator: group FA 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
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).
Other Names:
Drug: 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).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Diuretic efficacy after 6h [6 hours after administration of the study-specific diuretic regimen]
urine- natrium concentration (mmol/L)
Secondary Outcome Measures
- Diuretic efficacy after 2h [2 hours after administration of the study-specific diuretic regimen]
urine- natrium concentration (mmol/L)
- Diuretic efficacy after 24h [24 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 Outcome Measures
- Safety Outcomes 1 [0-24 hours after administration of the study-specific diuretic regimen]
Hypotension (SBP< 90 mmHg) with symptoms or requiring therapeutic intervention
- Safety Outcomes 2 [0-24 hours after administration of the study-specific diuretic regimen]
Increase in serum creatinine >50% from baseline
- 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)
Eligibility Criteria
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 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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Stadtspital Zürich
- Ospedale Regionale di Lugano
Investigators
- Principal Investigator: Mattia Arrigo, PD, Dr. med., City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P-Value-AHF