NCT04606927: PUSH-AHF

Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure

Completed NA Results posted Last updated 22 April 2024

What this trial tests

NA trial testing Natriuresis in Heart Failure Acute in 310 participants. Completed in 1 June 2023.

Timeline

1 February 2021

Primary endpoint
9 May 2023

1 June 2023

Quick facts

Lead sponsor	University Medical Center Groningen
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	310
Start date	1 February 2021
Primary completion	9 May 2023
Estimated completion	1 June 2023
Sites	1 location across Netherlands

Drugs / interventions tested

• Natriuresis — full drug profile →

Conditions studied

• Heart Failure Acute — all drugs for Heart Failure Acute →

Sponsor

University Medical Center Groningen

Who can join

18 and older, any sex, with Heart Failure Acute. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Total Natriuresis After 24 Hours Primary · 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).

Group	Value	95% CI
Natriuresis Guided Treatment	409	± 178
Standard of Care	345	± 202

First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days Primary · 180 days

Group	Value	95% CI
Natriuresis Guided Treatment	46
Standard of Care	50

Adverse events — posted to ClinicalTrials.gov

Time frame: During the study period (6 months). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Natriuresis Guided Treatment

Serious: 60/150 (40%)

Deaths: 29/150

Standard of Care

Serious: 70/160 (44%)

Deaths: 33/160

Serious adverse events (1 terms)

Reaction	System	Natriuresis Guided Treatment	Standard of Care
Diverse	Cardiac disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Natriuresis Guided Treatment	Standard of Care
Other	Cardiac disorders	—	—

Most-reported serious reactions: Diverse.

Data from ClinicalTrials.gov NCT04606927 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial.
   Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, et al · · 2023 · cited 115× · PMID 37640861 · DOI 10.1038/s41591-023-02532-z
2. Worsening renal function in acute heart failure in the context of diuretic response.
   Emmens JE, Ter Maaten JM, Matsue Y, Figarska SM, et al · · 2022 · cited 55× · PMID 34786794 · DOI 10.1002/ejhf.2384
3. Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial.
   Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, et al · · 2022 · cited 52× · PMID 34791756 · DOI 10.1002/ejhf.2385
4. Spot urinary sodium as a prognostic marker for mortality in patients with acute decompensated heart failure
   Londoño JM, Betancur KJ, Fonseca L, Fonseca P, et al · · 2023 · cited 2× · PMID 38207157 · DOI 10.7705/biomedica.6920
5. Mechanical Preload Reduction: Harnessing a Cornerstone of Heart Failure Management to Improve Clinical Outcomes.
   Kapur NK, Kanwar MK, Yousefzai R, Bhimiraj A, et al · · 2024 · cited 1× · PMID 38829983 · DOI 10.1097/mat.0000000000002240
6. Diuretic Resistance Risk and the Efficacy of Natriuresis-Guided Diuretic Therapy in Acute Heart Failure: Post Hoc Analysis From the PUSH-AHF Trial.
   Zonneveld LEEC, Pandey A, Beldhuis IE, van der Meer P, et al · · 2026 · PMID 41893376 · DOI 10.1016/j.jchf.2026.103017
7. Outpatient loop diuretic use and the effect of natriuresis-guided diuretic therapy: A prespecified sub-analysis of the PUSH-AHF study.
   Zonneveld LEEC, Beldhuis IE, Qin H, van Veldhuisen DJ, et al · · 2025 · PMID 41159496 · DOI 10.1002/ejhf.70080
8. The War of Attrition on Diuretic Resistance: We Need to Open a Third Front.
   Kazory A. · · 2023 · PMID 37640018 · DOI 10.1159/000533478