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

• ClinicalTrials.gov Identifier: NCT04606927
• Recruitment Status: Completed
• First Posted: October 28, 2020
• Results First Posted: April 22, 2024
• Last Update Posted: April 22, 2024
• Sponsor: University Medical Center Groningen
• Information provided by (Responsible Party): Jozine ter Maaten, University Medical Center Groningen

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure Acute	Other: Natriuresis	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: May 9, 2023
• Actual Study Completion Date: June 1, 2023

Arms and Interventions

Arm	Intervention/treatment
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.
No Intervention: Standard of care

Outcome Measures

Primary Outcome Measures :

1. Total Natriuresis After 24 Hours [ Time Frame: 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).
2. First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days [ Time Frame: 180 days ]

Secondary Outcome Measures :

1. 48-hours Natriuresis [ Time Frame: 48 hours ]
   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).
2. 72-hours Natriuresis [ Time Frame: 72 hours ]
   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).
3. Length of Hospital Stay [ Time Frame: Variable ]
   Number of days of the index hospitalization
4. Percentage Change in NT-proBNP at 48 Hours [ Time Frame: 48 hours ]
   Relative NT-proBNP change (%) after 48 hours compared with baseline
5. Percentage Change in NT-proBNP at 72 Hours [ Time Frame: 72 hours ]
   Relative NT-proBNP change (%) after 72 hours compared with baseline

Other Outcome Measures:

1. Safety Endpoint: Doubling of Serum Creatinine at 24 Hours [ Time Frame: 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.
2. Safety Endpoint: Doubling of Serum Creatinine at 48 Hours [ Time Frame: 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.
3. Worsening Heart Failure [ Time Frame: During the index hospitalization (variable) ]
   The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9713GZ

Sponsors and Collaborators

University Medical Center Groningen

  Study Documents (Full-Text)

Documents provided by Jozine ter Maaten, University Medical Center Groningen:

Study Protocol  [PDF] October 17, 2021

Statistical Analysis Plan  [PDF] May 30, 2023

More Information

• Responsible Party: Jozine ter Maaten, Principle investigator, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT04606927
• Other Study ID Numbers: 2020000710
• First Posted: October 28, 2020
• Results First Posted: April 22, 2024
• Last Update Posted: April 22, 2024
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jozine ter Maaten, University Medical Center Groningen:

loop diuretics; natriuresis

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases