Heart Failure
Conditions
Keywords
loop diuretics, heart failure, natriuresis, urinary analysis
Brief summary
The primary objective of this study is to assess whether the urinary sodium/creatinine or chloride/creatinine ratio might predict successful downtitration of loop diuretics in patients with stable heart failure without clinical signs of volume overload. In addition, this study will provide information on loop diuretic efficiency and urinary electrolyte composition after intake of diuretics in stable outpatients with heart failure.
Interventions
DEVICEWeight monitoring
The body weight of patients is measured each morning in identical conditions on the same balance during 7 days
DRUGLoop diuretic downtitration
The patient's total daily maintenance dose of loop diuretics is downtitrated during 7 consecutive days. In case of a total daily maintenance dose ≤40 mg furosemide OR ≤1 mg bumetanide OR ≤20 mg torsemide, the loop diuretic is completely stopped. In case of a total daily maintenance dose \>40 mg furosemide OR \>1 mg bumetanide OR \>20 mg torsemide, the loop diuretic dose is halved.
Sponsors
Ziekenhuis Oost-Limburg
Hasselt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a left ventricular ejection fraction \<40% or has been previously hospitalized with a primary diagnosis of heart failure * Patient receives a daily maintenance dose of loop diuretics
Exclusion criteria
* Patient was hospitalized for heart failure \<3 months before study inclusion * The maintenance dose of loop diuretics was changed \<3 months before study inclusion * The maintenance dose of renin-angiotensin-aldosterone system blockers or beta-blocker medication was changed \<3 months before study inclusion * Cardiac resynchronization therapy (CRT) was initiated \<3 months before study inclusion * At the moment of inclusion, the patient has either one of the following signs of volume overload: lower leg edema +2/4, ascites, lung congestion * Patient is not able to measure his/her weight safely and correct at home
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Downtitration of Loop Diuretics (no Weight Increase >1,5 kg) | 7 days after baseline | After baseline evaluation, loop diuretics are temporarily downtitrated or stopped for 7 consecutive days. The patient is instructed to measure his/her weight in the morning of these days, immediately after waking up, on the same balance. In case of weight increase \>1,5 kg, the original dose of diuretics is restored. To check this, patients are contacted by phone after 3 and 7 days. If the patient has not gained \>1,5 kg of weight after 7 days, loop diuretics are considered to be successfully downtitrated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 30 days after baseline | — |
| Number of Participants Rehospitalized for Heart Failure | 30 days after baseline | Unplanned hospital admission for symptoms of congestion and/or low output heart failure requiring either intravenous therapy and/or increase of oral diuretics. |
| Number of Participants Requiring a Dose Increase in Loop Diuretics | 30 days after baseline | Dose increase of oral maintenance therapy with loop diuretics compared to the final dose achieved in the study 7 days after baseline. |
| Weight Change | 7 days after baseline | Weight change \[kg\] 7 days after baseline compared to baseline weight. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rehospitalization for Heart Failure | 6 months after baseline | Unplanned hospital admission for symptoms of congestion and/or low output heart failure requiring either intravenous therapy and/or increase of oral diuretics. |
| Weight Change | 30 days after baseline | Weight change \[kg\] 30 days after baseline compared to weight 7 days after baseline (after achieving the final dose of loop diuretics). |
| NYHA Functional Class | 30 days after baseline | The patient is contacted by phone 30 days after baseline and NYHA functional class is assessed by a study investigator. |
| Dose Increase of Loop Diuretics | 6 months after baseline | Dose increase of oral maintenance therapy with loop diuretics compared to the final dose achieved in the study 7 days after baseline. |
| Self-reported Orthopnea | 30 days after baseline | The patient is contacted by phone 30 days after baseline and asked for self-reported orthopnea. |
| Self-reported Lower Leg Edema | 30 days after baseline | The patient is contacted by phone 30 days after baseline and asked for self-reported presence of lower leg edema. |
| New York Heart Association (NYHA) Functional Class | 30 days after baseline | NYHA class is a semi-quantitative measurement of functional capacity on a scale from 1 to 4: 1. No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). 2. Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). 3. Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. 4. Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. For the purpose of this outcome parameter, the patient is contacted by phone 30 days after baseline and NYHA functional class is assessed by a study investigator. |
| All-cause Mortality | 6 months after baseline | — |
Countries
Belgium
Participant flow
Recruitment details
Outpatient cardiology clinic of a single tertiary centre (Ziekenhuis Oost-Limburg, Genk, Belgium) between December, 2014, and February, 2016.
Participants by arm
| Arm | Count |
|---|---|
| Loop Diuretic Downtitration Scheduled downtitration of maintenance loop diuretic dose while monitoring weight
Weight monitoring: The body weight of patients is measured each morning in identical conditions on the same balance during 7 days
Loop diuretic downtitration: The patient's total daily maintenance dose of loop diuretics is downtitrated during 7 consecutive days.
In case of a total daily maintenance dose ≤40 mg furosemide OR ≤1 mg bumetanide OR ≤20 mg torsemide, the loop diuretic is completely stopped.
In case of a total daily maintenance dose \>40 mg furosemide OR \>1 mg bumetanide OR \>20 mg torsemide, the loop diuretic dose is halved. | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Loop Diuretic Downtitration |
|---|---|
| Age, Continuous | 73 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 50 Participants |
| Region of Enrollment Belgium | 50 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 50 |
| other Total, other adverse events | 0 / 50 |
| serious Total, serious adverse events | 1 / 50 |
Outcome results
Primary
Number of Participants With Successful Downtitration of Loop Diuretics (no Weight Increase >1,5 kg)
After baseline evaluation, loop diuretics are temporarily downtitrated or stopped for 7 consecutive days. The patient is instructed to measure his/her weight in the morning of these days, immediately after waking up, on the same balance. In case of weight increase \>1,5 kg, the original dose of diuretics is restored. To check this, patients are contacted by phone after 3 and 7 days. If the patient has not gained \>1,5 kg of weight after 7 days, loop diuretics are considered to be successfully downtitrated.
Time frame: 7 days after baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | Number of Participants With Successful Downtitration of Loop Diuretics (no Weight Increase >1,5 kg) | 37 Participants |
Secondary
All-cause Mortality
Time frame: 30 days after baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | All-cause Mortality | 1 Participants |
Secondary
Number of Participants Rehospitalized for Heart Failure
Unplanned hospital admission for symptoms of congestion and/or low output heart failure requiring either intravenous therapy and/or increase of oral diuretics.
Time frame: 30 days after baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | Number of Participants Rehospitalized for Heart Failure | 1 Participants |
Secondary
Number of Participants Requiring a Dose Increase in Loop Diuretics
Dose increase of oral maintenance therapy with loop diuretics compared to the final dose achieved in the study 7 days after baseline.
Time frame: 30 days after baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | Number of Participants Requiring a Dose Increase in Loop Diuretics | 1 Participants |
Secondary
Weight Change
Weight change \[kg\] 7 days after baseline compared to baseline weight.
Time frame: 7 days after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Loop Diuretic Downtitration | Weight Change | 0.502 kg | Standard Deviation 1.101 |
Other Pre-specified
All-cause Mortality
Time frame: 6 months after baseline
Population: The study was terminated after every participant reached the 30-day follow-up point because of slow recruitment and a lack of funding to complete further follow-up
Other Pre-specified
Dose Increase of Loop Diuretics
Dose increase of oral maintenance therapy with loop diuretics compared to the final dose achieved in the study 7 days after baseline.
Time frame: 6 months after baseline
Other Pre-specified
New York Heart Association (NYHA) Functional Class
NYHA class is a semi-quantitative measurement of functional capacity on a scale from 1 to 4: 1. No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). 2. Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). 3. Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. 4. Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. For the purpose of this outcome parameter, the patient is contacted by phone 30 days after baseline and NYHA functional class is assessed by a study investigator.
Time frame: 30 days after baseline
Population: 1 patient who died before the 30-day follow-up could not be assessed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Loop Diuretic Downtitration | New York Heart Association (NYHA) Functional Class | 1.41 units on a scale from 1 to 4 | Standard Deviation 0.57 |
Other Pre-specified
NYHA Functional Class
The patient is contacted by phone 30 days after baseline and NYHA functional class is assessed by a study investigator.
Time frame: 30 days after baseline
Other Pre-specified
Rehospitalization for Heart Failure
Unplanned hospital admission for symptoms of congestion and/or low output heart failure requiring either intravenous therapy and/or increase of oral diuretics.
Time frame: 6 months after baseline
Other Pre-specified
Self-reported Lower Leg Edema
The patient is contacted by phone 30 days after baseline and asked for self-reported presence of lower leg edema.
Time frame: 30 days after baseline
Population: 1 patient who died before the 30-day follow-up could not be assessed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | Self-reported Lower Leg Edema | 1 Participants |
Other Pre-specified
Self-reported Lower Leg Edema
The patient is contacted by phone 30 days after baseline and asked for self-reported presence of lower leg edema.
Time frame: 30 days after baseline
Other Pre-specified
Self-reported Orthopnea
The patient is contacted by phone 30 days after baseline and asked for self-reported orthopnea.
Time frame: 30 days after baseline
Other Pre-specified
Self-reported Orthopnea
The patient is contacted by phone 30 days after baseline and asked for self-reported orthopnea.
Time frame: 30 days after baseline
Population: 1 patient who died before the 30-day follow-up could not be assessed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Loop Diuretic Downtitration | Self-reported Orthopnea | 5 Participants |
Other Pre-specified
Weight Change
Weight change \[kg\] 7 days after baseline compared to baseline weight.
Time frame: 7 days after baseline
Other Pre-specified
Weight Change
Weight change \[kg\] 30 days after baseline compared to weight 7 days after baseline (after achieving the final dose of loop diuretics).
Time frame: 30 days after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Loop Diuretic Downtitration | Weight Change | -0.261 kg | Standard Deviation 1.391 |