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

Tracking Information

• First Submitted Date: October 18, 2020
• First Posted Date: October 28, 2020
• Results First Submitted Date: November 1, 2023
• Results First Posted Date: April 22, 2024
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: May 9, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2023)

• 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).
• First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days [ Time Frame: 180 days ]

Original Primary Outcome Measures (submitted: October 22, 2020)

• 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).
• First occurrence of all-cause mortality or heart failure rehospitalization after 180 days [ Time Frame: 180 days ]

Current Secondary Outcome Measures (submitted: November 1, 2023)

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

Original Secondary Outcome Measures (submitted: October 22, 2020)

• 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).
• 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).
• Length of hospital stay [ Time Frame: Variable ]
  Number of days of the index hospitalization
• Percentage change in NT-proBNP at 48 hours [ Time Frame: 48 hours ]
  Relative NT-proBNP change (%) after 48 hours compared to baseline
• Percentage change in NT-proBNP at 72 hours [ Time Frame: 72 hours ]
  Relative NT-proBNP change (%) after 72 hours compared to baseline

Current Other Pre-specified Outcome Measures (submitted: November 1, 2023)

• 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.
• 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.
• 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.

Original Other Pre-specified Outcome Measures (submitted: October 22, 2020)

• Safety endpoint: doubling of serum creatinine at 24 hours [ Time Frame: 24 hours ]
  The first safety endpoint is defined as a doubling of serum creatinine at 24 hours compared to baseline serum creatinine.
• Safety endpoint: doubling of serum creatinine at 48 hours [ Time Frame: 48 hours ]
  The second safety endpoint is defined as a doubling of serum creatinine at 48 hours compared to baseline serum creatinine.

Descriptive Information

• Brief Title: Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure
• Official Title: Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure
• 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Heart Failure Acute

Intervention

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.

Study Arms

• Active Comparator: Natriuresis guided treatment
  Intervention: Other: Natriuresis
• No Intervention: Standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 22, 2020): 310
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 1, 2023
• Actual Primary Completion Date: May 9, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04606927
• Other Study ID Numbers: 2020000710
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jozine ter Maaten, University Medical Center Groningen
• Original Responsible Party: Same as current
• Current Study Sponsor: University Medical Center Groningen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Medical Center Groningen
• Verification Date: November 2023