Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure (PUSH-AHF)

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure Acute
• Intervention / Treatment: Other: Natriuresis

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥ 18 years of age

2. 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

3. Requirement of intravenous diuretic use

Exclusion Criteria:

1. Dyspnoea primarily due to non-cardiac causes
2. Patients with severe renal impairment receiving dialysis or requiring ultrafiltration
3. Inability to follow instructions
4. Any other medical conditions that may put the patient at risk or influence study results in the investigator's opinion, or that the investigator deems unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care
Active Comparator: Natriuresis guided treatment	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Other Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: October 18, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: loop diuretics; natriuresis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2020000710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No