| Primary | Mortality, Days in Hospital & Decongestion | 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:
- 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.
- 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.
- 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.
| | Posted | | Number | | % wins | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
| | | Title | Denominators | Categories |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | General pairwaise comparison | | 0.357 | | Net treatment benefit | 10.5 | | | 2-Sided | 95 | -11.9 | 31.9 | | | | | Superiority | | |
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| Secondary | Renal Safety Endpoint | 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. | | Posted | | Count of Participants | | Participants | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
|
| Secondary | Hemodynamic Safety Endpoint | 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. | | Posted | | Count of Participants | | Participants | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
|
| Secondary | Natriuretic Peptide Change After 30 Days | Relative NT-proBNP change from baseline to 30 days after randomisation [%]. | This endpoint could not be assessed in patients who died (n=3 in the intervention arm and n=4 in the control arm). In addition, 1 patient in the intervention arm withdrew consent during follow-up. Vital status could be assessed, but no blood sample was available for this patient. Finally, 5 blood samples were missing in the control group because patients were unable to physically attend the final follow-up visit. | Posted | | Mean | Standard Deviation | % of change from baseline | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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| Secondary | Cancer Antigen 125 (CA125) Change After 30 Days | Relative cancer antigen 125 (CA125) change from baseline to 30 days after randomisation [%]. | This endpoint could not be assessed in patients who died (n=3 in the intervention arm and n=4 in the control arm). In addition, 1 patient in the intervention arm withdrew consent during follow-up. Vital status could be assessed, but no blood sample was available for this patient. Finally, 5 blood samples were missing in the control group because patients were unable to physically attend the final follow-up visit. | Posted | | Mean | Standard Deviation | % of change from baseline | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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| Secondary | Number of Participants With Successful Clinical Decongestion | 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. | This endpoint was not be assessed in patients who died (n=3 in the intervention arm and n=4 in the control arm). One edema score was missing in the control group and could not be retrieved, precluding the assessment of decongestion success. | Posted | | Count of Participants | | Participants | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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| Secondary | Length of Intravenous Diuretic Therapy | Number of consecutive days from randomization during the index admission on which intravenous diuretic therapy was administered. | This endpoint was not be assessed in patients who died (n=3 in the intervention arm and n=4 in the control arm). | Posted | | Median | Inter-Quartile Range | days | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
|
| Secondary | Overall Well-being After Decongestion | 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). | This endpoint could not be assessed in patients who died before switching to oral diuretics (n=1 in the intervention group and n=3 in the control group). | Posted | | Count of Participants | | Participants | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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| Secondary | Length of the Index Hospital Admission | Length of the index hospital admission [days]. | This endpoint was not be assessed in patients who died (n=3 in the intervention arm and n=4 in the control arm). | Posted | | Median | Inter-Quartile Range | days | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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| Secondary | Number of Participants Who Are Death, or Have a Non-elective Hospital Admission or Non-elective Medical Contact | Number of participants who are death, or have a non-elective hospital admission or non-elective medical contact | One patient in the intervention arm withdrew consent during follow-up. Vital status could be assessed, but not data on hospitalizations or medical contacts. Therefore the overall number of participants analyzed is 1 lower than for the primary endpoint. | Posted | | Count of Participants | | Participants | | 30 days | | | | ID | Title | Description |
|---|
| OG000 | Intervention Arm | Application of a standardized diuretic schedule with following key components:
- Serial post-diuretic spot urine sodium (UNa) assessment
- Loop diuretic dosing according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
- Full nephron blockade for diuretic resistance
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics
| | OG001 | Control Arm | 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. Usual AHF care: 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. |
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