Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment
- Conditions
- Acute Heart FailureDiuretics Drug Reactions
- Interventions
- Diagnostic Test: UNa measurement after intravenous loop diuretic bolusOther: Usual AHF careOther: Maintenance infusionOther: Intravenous hypertonic salineOther: Switch to oral diuretic therapy
- Registration Number
- NCT05411991
- Lead Sponsor
- Vrije Universiteit Brussel
- Brief Summary
This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.
- Detailed Description
Key interventions are:
* Assessment of UNa in spot urine samples after every bolus administration of loop diuretics with continuation of intravenous diuretics until resolution of clinical signs of fluid overload AND UNa \<80 mmol/L
* Dosing of loop diuretic bolus according to estimated glomerular filtration rate (eGFR)
* Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia (\>145 mmol/L) or metabolic acidosis (bicarbonate \<22 mmol/L)
* Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia (\>145 mmol/L)
* Switch to full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload
* Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during diuretic therapy with intravenous diuretics
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 107
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention arm Intravenous acetazolamide 500 mg OD Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Intravenous bumetanide TID Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Intravenous canrenoate 200 mg OD Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Oral potassium supplements Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Oral chlorthalidone OD Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm UNa measurement after intravenous loop diuretic bolus Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Switch to oral diuretic therapy Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Intervention arm Maintenance infusion Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Control arm Usual AHF care Usual care for AHF. It is recommended to administer an intravenous loop diuretic dose at least BID (or through continuous infusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered in an optimal volume status as is recommended by current guidelines. Urine electrolyte assessment in the control arm is not allowed as it is a key component of the studied intervention. Intervention arm Intravenous hypertonic saline Application of a standardized diuretic schedule with following key components: * UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa \<80 mmol/L * Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia * Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
- Primary Outcome Measures
Name Time Method Mortality, Days in Hospital & Decongestion 30 days The net treatment benefit is calculated for the hierarchical composite primary endpoint. Every patient from the intervention group is pair-wise compared with each patient from the control group to declare a winner or tie. The following criteria are sequentially assessed to declare a winner or a tie:
1. Any subject surviving until 30 days after randomization wins from a subject who died. If both subjects did not survive until day 30, there is a tie.
2. In a pair of subjects, both surviving up till day 30, the subject with the highest number of days alive and out of hospital or care facility during the 30-day follow-up window is declared the winner.
3. In a pair of subjects, both surviving up till day 30 with the same number of days alive and out of hospital/care facility, the subject with the greatest relative reduction in NTproBNP from baseline is the winner (rounded to the closest percentage with a minimal difference of 5%). If the difference is \<5%, there is a tie.
- Secondary Outcome Measures
Name Time Method Renal Safety Endpoint 30 days Number of patients with doubling of the serum creatinine or plasma cystatin C value compared to baseline with an absolute value \>2 mg/dL or \>2 mg/L, respectively, or the need for ultrafiltration and/or renal replacement therapy during the index hospital admission.
Hemodynamic Safety Endpoint 30 days Number of patients with a ystolic blood pressure \<90 mmHg or mean arterial pressure \<65 mmHg or need for vasopressors and/or inotropes during the index hospital admission.
Natriuretic Peptide Change After 30 Days 30 days Relative NT-proBNP change from baseline to 30 days after randomisation \[%\].
Cancer Antigen 125 (CA125) Change After 30 Days 30 days Relative cancer antigen 125 (CA125) change from baseline to 30 days after randomisation \[%\].
Number of Participants With Successful Clinical Decongestion 30 days Number of participants with no more than trace edema, absence of jugular venous distension and no rales upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.
Length of Intravenous Diuretic Therapy 30 days Number of consecutive days from randomization during the index admission on which intravenous diuretic therapy was administered.
Overall Well-being After Decongestion 30 days Five-point Likert scale for overall well-being upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol and compared with the moment of randomisation (5: much improved/4: slightly improved/3: neutral/2: slightly worse/1: much worse).
Length of the Index Hospital Admission 30 days Length of the index hospital admission \[days\].
Number of Participants Who Are Death, or Have a Non-elective Hospital Admission or Non-elective Medical Contact 30 days Number of participants who are death, or have a non-elective hospital admission or non-elective medical contact
Trial Locations
- Locations (2)
University Hospital Brussels
🇧🇪Jette, Brussels, Belgium
Jessa Hospital
🇧🇪Hasselt, Limburg, Belgium
University Hospital Brussels🇧🇪Jette, Brussels, Belgium