Heart Failure Acute
Conditions
Keywords
loop diuretics, natriuresis
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.
Interventions
OTHERNatriuresis
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.
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days | 180 days | — |
| Total Natriuresis After 24 Hours | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 72-hours Natriuresis | 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 | Variable | Number of days of the index hospitalization |
| 48-hours Natriuresis | 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). |
| Percentage Change in NT-proBNP at 48 Hours | 48 hours | Relative NT-proBNP change (%) after 48 hours compared with baseline |
| Percentage Change in NT-proBNP at 72 Hours | 72 hours | Relative NT-proBNP change (%) after 72 hours compared with baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Endpoint: Doubling of Serum Creatinine at 48 Hours | 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. |
| Safety Endpoint: Doubling of Serum Creatinine at 24 Hours | 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. |
| Worsening Heart Failure | During the index hospitalization (variable) | The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 150 |
| Standard of Care Standard of care | 160 |
| Total | 310 |
Baseline characteristics
| Characteristic | Natriuresis Guided Treatment | Total | Standard of Care |
|---|---|---|---|
| Age, Continuous | 74 years | 74 years | 74 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) White | 142 Participants | 297 Participants | 155 Participants |
| Region of Enrollment Netherlands | 150 participants | 310 participants | 160 participants |
| Sex: Female, Male Female | 61 Participants | 138 Participants | 77 Participants |
| Sex: Female, Male Male | 89 Participants | 172 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 150 | 33 / 160 |
| other Total, other adverse events | 0 / 150 | 0 / 160 |
| serious Total, serious adverse events | 60 / 150 | 70 / 160 |
Outcome results
Primary
First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Natriuresis Guided Treatment | First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days | 46 Participants |
| Standard of Care | First Occurrence of All-cause Mortality or Heart Failure Rehospitalization After 180 Days | 50 Participants |
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).
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natriuresis Guided Treatment | Total Natriuresis After 24 Hours | 409 mmol | Standard Deviation 178 |
| Standard of Care | Total Natriuresis After 24 Hours | 345 mmol | Standard Deviation 202 |
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).
Time frame: 48 hours
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).
Time frame: 72 hours
Secondary
Length of Hospital Stay
Number of days of the index hospitalization
Time frame: Variable
Secondary
Percentage Change in NT-proBNP at 48 Hours
Relative NT-proBNP change (%) after 48 hours compared with baseline
Time frame: 48 hours
Secondary
Percentage Change in NT-proBNP at 72 Hours
Relative NT-proBNP change (%) after 72 hours compared with baseline
Time frame: 72 hours
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.
Time frame: 24 hours
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.
Time frame: 48 hours
Other Pre-specified
Worsening Heart Failure
The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization.
Time frame: During the index hospitalization (variable)