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Administration of loop diuretics to achieve decongestion is the current cornerstone of therapy for acute heart failure. Unfortunately, there is a lack of evidence of how to guide diuretic treatment. Recently, urinary sodium, as a response measure of diuretic response, has been proposed as a target for therapy. The hypothesis of this study is that natriuresis guided therapy in patients with acute heart failure will improve diuretic response, decongestion, and reduce length of hospital stay, as well as heart failure rehospitalisations.
Objective: To assess the effect of natriuresis guided therapy in acute heart failure to improve diuretic response, decongestion, and clinical outcomes
Study design: Randomised, controlled, open label study
Study population: 310 patients admitted with the primary diagnosis of acute heart failure requiring intravenous loop diuretics.
Intervention: natriuresis guided treatment versus standard of care
Main study parameters/endpoints:
Co-primary outcome: total natriuresis after 24 hours, and first occurrence of all-cause mortality or heart failure rehospitalisation at 6 months Secondary outcomes: 48- and 72-hours natriuresis, length of hospital stay, percentage change in NT-proBNP at 48 and 72 hours.
Safety endpoint: doubling of serum creatinine at 24 or 48 hours, worsening heart failure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Natriuresis guided treatment | Active Comparator |
| |
| Standard of care | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Natriuresis | Other | Patients with insufficient decongestive response based on natriuresis (in the active arm) will be eligible for treatment adjustments according to the natriuresis guided treatment algorithm. |
| Measure | Description | Time Frame |
|---|---|---|
| Total Natriuresis After 24 Hours | The first component of the co-primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 hours after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). | 24 hours |
| First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days | 180 days |
| Measure | Description | Time Frame |
|---|---|---|
| 48-hours Natriuresis | 48-hour natriuresis will be assessed by collecting urine for a second period of 24 hours after the first 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). | 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Endpoint: Doubling of Serum Creatinine at 24 Hours | The first safety endpoint is defined as number of patients with a doubling of serum creatinine at 24 hours compared with baseline serum creatinine. | 24 hours |
| Safety Endpoint: Doubling of Serum Creatinine at 48 Hours |
Inclusion Criteria:
Male or female ≥ 18 years of age
Primary diagnosis of acute /decompensated heart failure as assessed by treating physician
a. Acute Heart failure can be de novo or exacerbation of known heart failure and diagnosis is based on criteria in the ESC HF guidelines
Requirement of intravenous diuretic use
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9713GZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41893376 | Derived | Zonneveld LEEC, Pandey A, Beldhuis IE, van der Meer P, Coster JE, Nieuwland W, Trullas JC, van Veldhuisen DJ, Voors AA, Damman K, Ter Maaten JM. Diuretic Resistance Risk and the Efficacy of Natriuresis-Guided Diuretic Therapy in Acute Heart Failure: Post Hoc Analysis From the PUSH-AHF Trial. JACC Heart Fail. 2026 Mar 26:103017. doi: 10.1016/j.jchf.2026.103017. Online ahead of print. | |
| 37640861 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Natriuresis Guided Treatment | Natriuresis: Patients with insufficient decongestive response based on natriuresis (in the active arm) will be eligible for treatment adjustments according to the natriuresis guided treatment algorithm. |
| FG001 | Standard of Care | Standard of care |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Natriuresis Guided Treatment | Natriuresis: Patients with insufficient decongestive response based on natriuresis (in the active arm) will be eligible for treatment adjustments according to the natriuresis guided treatment algorithm. |
| BG001 | Standard of Care |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Natriuresis After 24 Hours | The first component of the co-primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 hours after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). | Posted | Mean | Standard Deviation | mmol | 24 hours |
|
During the study period (6 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Natriuresis Guided Treatment | Natriuresis: Patients with insufficient decongestive response based on natriuresis (in the active arm) will be eligible for treatment adjustments according to the natriuresis guided treatment algorithm. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diverse | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Other | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jozine ter Maaten | University Medical Center Groningen | 0503616161 | j.m.ter.maaten@umcg.nl |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 17, 2021 | Nov 1, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 30, 2023 | Oct 31, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009318 | Natriuresis |
| ID | Term |
|---|---|
| D004231 | Diuresis |
| D014553 | Urinary Tract Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
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| 72-hours Natriuresis |
72-hour natriuresis will be assessed by collecting urine for a third period of 24 hours after the second 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). |
| 72 hours |
| Length of Hospital Stay | Number of days of the index hospitalization | Variable |
| Percentage Change in NT-proBNP at 48 Hours | Relative NT-proBNP change (%) after 48 hours compared with baseline | 48 hours |
| Percentage Change in NT-proBNP at 72 Hours | Relative NT-proBNP change (%) after 72 hours compared with baseline | 72 hours |
The second safety endpoint is defined as the number of patients with a doubling of serum creatinine at 48 hours compared with baseline serum creatinine. |
| 48 hours |
| Worsening Heart Failure | The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization. | During the index hospitalization (variable) |
| Derived |
| Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Postmus D, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023 Oct;29(10):2625-2632. doi: 10.1038/s41591-023-02532-z. Epub 2023 Aug 28. |
Standard of care |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Standard of care
|
|
| Primary | First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days | Posted | Count of Participants | Participants | 180 days |
|
|
|
| Secondary | 48-hours Natriuresis | 48-hour natriuresis will be assessed by collecting urine for a second period of 24 hours after the first 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). | Not Posted | 48 hours | Participants |
| Secondary | 72-hours Natriuresis | 72-hour natriuresis will be assessed by collecting urine for a third period of 24 hours after the second 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). | Not Posted | 72 hours | Participants |
| Secondary | Length of Hospital Stay | Number of days of the index hospitalization | Not Posted | Variable | Participants |
| Secondary | Percentage Change in NT-proBNP at 48 Hours | Relative NT-proBNP change (%) after 48 hours compared with baseline | Not Posted | 48 hours | Participants |
| Secondary | Percentage Change in NT-proBNP at 72 Hours | Relative NT-proBNP change (%) after 72 hours compared with baseline | Not Posted | 72 hours | Participants |
| Other Pre-specified | Safety Endpoint: Doubling of Serum Creatinine at 24 Hours | The first safety endpoint is defined as number of patients with a doubling of serum creatinine at 24 hours compared with baseline serum creatinine. | Not Posted | 24 hours | Participants |
| Other Pre-specified | Safety Endpoint: Doubling of Serum Creatinine at 48 Hours | The second safety endpoint is defined as the number of patients with a doubling of serum creatinine at 48 hours compared with baseline serum creatinine. | Not Posted | 48 hours | Participants |
| Other Pre-specified | Worsening Heart Failure | The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization. | Not Posted | During the index hospitalization (variable) | Participants |
| 29 |
| 150 |
| 60 |
| 150 |
| 0 |
| 150 |
| EG001 | Standard of Care | Standard of care | 33 | 160 | 70 | 160 | 0 | 160 |
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