Heart Failure; With Decompensation
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of ultrahigh dose diuretics compared to standard dose diuretics over 24 hours in patients with decompensated heart failure.
Interventions
DRUGBumetanide
Bumetanide will be administered via intravenous (IV) infusion at a dose of 12.5 mg two times a day (BID) for 2 doses total within 24 hours.
DRUGFurosemide
Furosemide will be administered via intravenous (IV) infusion at usual doses (twice the home dose of oral daily diuretic in furosemide equivalents) administered as 2 doses total within 24 hours. Furosemide equivalents will be considered as follows (40 mg of intravenous furosemide = 1 mg oral bumetanide or 40 mg of torsemide or 80 mg of oral furosemide consistent with prior literature). The lowest dose of furosemide administered during the study will be 40 mg IV two times a day (BID) and the maximum dose will be 100 mg IV BID.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of decompensated heart failure receiving intravenous diuretics * Ability to provide informed consent
Exclusion criteria
* Patients on home inotrope medications * Patients with Chronic Kidney disease stage V and end stage renal failure on dialysis * Patients lacking the capacity to consent for themselves * Known pregnancy or breastfeeding mothers * Complex congenital heart disease * Allergy to furosemide or bumetanide * Respiratory failure requiring non-invasive ventilation (CPAP/BiPAP) or invasive mechanical ventilatory support at the time of randomization * Hypotension with systolic blood pressure \<80 mm Hg at the time of randomization * Acute coronary syndrome * Sustained Ventricular tachycardia requiring treatment in the last 48 hours * Patients weighing ≤ 40 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Output | 24 hours | The total volume of urine produced in milliliters (mL) over 24 hours after initiation of intravenous diuretic. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NT-proBNP | Baseline, 24 hours | Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic. |
| Change in Urine Sodium Excretion | Baseline, 24 hours | Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic. |
| Change in Apnea-hypopnea Index | Baseline, 24 hours | The apnea-hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep which is an indicator of severity of sleep apnea AHI will be measured using a Watch Pat or Nox device at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Iohexol Glomerular Filtration Rate (GFR) | Baseline, 24 hours | Renal or kidney function was measured by GFR determined by Iohexol clearance. Iohexol GFR will be measured at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Peripheral Vein Pressure | Baseline, 24 hours | Peripheral vein pressure (mm Hg) will be recorded from existing IV lines through pressure transducer monitoring at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Cardiac Output | Baseline, 24 hours | Cardiac output (L/min) is the total volume of blood moved by the heart per minute and will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Body Weight | Baseline, 24 hours | Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic. |
| Change in Right Atrial (RA) Pressure | Baseline, 24 hours | RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Left Atrial (LA) Strain | Baseline, 24 hours | LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Left Ventricular (LV) Global Longitudinal Strain | Baseline, 24 hours | LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in Right Ventricular (RV) Global Longitudinal Strain | Baseline, 24 hours | RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
| Change in E/e' | Baseline, 24 hours | E/e' will be assessed using echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. It is defined as the ratio of peak early diastolic mitral inflow velocity (E) and peak early diastolic mitral annular velocity (e'). |
| Change in Estimated Right Ventricular (RV) Systolic Pressure | Baseline, 24 hours | Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ultra-high Dose Diuretic Group Subjects with decompensated heart failure requiring hospitalization received IV bumetanide.
Bumetanide: Bumetanide was administered via intravenous (IV) infusion at a dose of 12.5 mg two times a day (BID) for 2 doses total within 24 hours. | 10 |
| Standard Dose Diuretic Group Subjects with decompensated heart failure requiring hospitalization received IV furosemide.
Furosemide: Furosemide was administered via intravenous (IV) infusion at usual doses (twice the home dose of oral daily diuretic in furosemide equivalents) administered as 2 doses total within 24 hours.
Furosemide equivalents were considered as follows (40 mg of intravenous furosemide = 1 mg oral bumetanide or 40 mg of torsemide or 80 mg of oral furosemide consistent with prior literature). The lowest dose of furosemide administered during the study was 40 mg IV two times a day (BID) and the maximum dose was 100 mg IV BID. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Ultra-high Dose Diuretic Group | Total | Standard Dose Diuretic Group |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 12.4 | 69 years STANDARD_DEVIATION 13 | 70.9 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 20 Participants | 10 Participants |
| 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 | 1 Participants | 2 Participants | 1 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment United States | 10 participants | 20 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Urine Output
The total volume of urine produced in milliliters (mL) over 24 hours after initiation of intravenous diuretic.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultra-high Dose Diuretic Group | Urine Output | 5283 mL | Standard Deviation 2976 |
| Standard Dose Diuretic Group | Urine Output | 2819 mL | Standard Deviation 1060 |
Secondary
Change in Apnea-hypopnea Index
The apnea-hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep which is an indicator of severity of sleep apnea AHI will be measured using a Watch Pat or Nox device at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Body Weight
Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultra-high Dose Diuretic Group | Change in Body Weight | -2.6 kg | Standard Deviation 3 |
| Standard Dose Diuretic Group | Change in Body Weight | -3.8 kg | Standard Deviation 3.3 |
Secondary
Change in Cardiac Output
Cardiac output (L/min) is the total volume of blood moved by the heart per minute and will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data was not technically feasible to obtain for 3 subjects in the Ultra-High Dose diuretic group for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultra-high Dose Diuretic Group | Change in Cardiac Output | -0.53 L/min | Standard Deviation 0.83 |
| Standard Dose Diuretic Group | Change in Cardiac Output | 0.29 L/min | Standard Deviation 1.5 |
Secondary
Change in E/e'
E/e' will be assessed using echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. It is defined as the ratio of peak early diastolic mitral inflow velocity (E) and peak early diastolic mitral annular velocity (e').
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Estimated Right Ventricular (RV) Systolic Pressure
Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Iohexol Glomerular Filtration Rate (GFR)
Renal or kidney function was measured by GFR determined by Iohexol clearance. Iohexol GFR will be measured at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Left Atrial (LA) Strain
LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Left Ventricular (LV) Global Longitudinal Strain
LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in NT-proBNP
Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultra-high Dose Diuretic Group | Change in NT-proBNP | 2898 pg/ml | Standard Deviation 7278 |
| Standard Dose Diuretic Group | Change in NT-proBNP | -1705 pg/ml | Standard Deviation 1712 |
Secondary
Change in Peripheral Vein Pressure
Peripheral vein pressure (mm Hg) will be recorded from existing IV lines through pressure transducer monitoring at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data was not collected for 1 subject in the Ultra-High dose diuretic group as the subject requested that peripheral vein pressure data not be collected on them.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultra-high Dose Diuretic Group | Change in Peripheral Vein Pressure | -10.9 mmHg | Standard Deviation 7.5 |
| Standard Dose Diuretic Group | Change in Peripheral Vein Pressure | -4 mmHg | Standard Deviation 3.1 |
Secondary
Change in Right Atrial (RA) Pressure
RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Right Ventricular (RV) Global Longitudinal Strain
RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a result, no data was collected for this outcome measure.
Secondary
Change in Urine Sodium Excretion
Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic.
Time frame: Baseline, 24 hours
Population: Data for this outcome measure was not collected for any participants. Upon study initiation, this outcome measure was not technically feasible to obtain with existing staffing and was therefore not performed. As a results, no data was collected for this outcome measure.