Heart Failure, Diastolic
Conditions
Keywords
Heart failure, diastolic, HFpEF, Diuretics, Dopamine
Brief summary
Heart Failure with preserved Ejection Fraction (HFPEF) accounts for 40-50% of all heart failure patients with a frequency of hospital admissions for acute decompensation and short and long term mortality similar to patients with heart failure with reduced ejection fraction (HFREF). Patients with HFPEF are often preload dependent and despite admission to the hospital for acute decompensated heart failure (ADHF), are typically difficult to diurese due to the development of acute kidney injury. No studies have been performed evaluating treatment strategies for these patients. The investigators hypothesize that changing the method of diuresis and/or the addition of low-dose dopamine for the treatment of ADHF in patients with HFPEF will reduce renal injury, resulting in a shorter length of stay, and decrease hospital readmissions over the ensuing year. This trial will randomize patients to either bolus or continuous infusion furosemide and then to either dopamine or no dopamine. The primary endpoint will be renal function at 72 hours as measured by change in Glomerular Filtration Rate (GFR). Secondary endpoints for readmission, functional capacity, quality of life, and amount of diuresis will also be collected.
Interventions
DRUGFurosemide
DRUGDopamine
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admission to Johns Hopkins Hospital for acute decompensated heart failure. * Patient ≥18 years of age * Estimated GFR of \> 15 milliliters/min/1.73m2 determined by the Modification of Diet in Renal Disease (MDRD) equation * Willingness to provide informed consent * Known ejection fraction by noninvasive testing of \> 50% within 12 months of admission to the hospital with no interval myocardial infarction since inclusion transthoracic echo, by history, or by ECG. * Negative pregnancy test in a female of child bearing potential * Willingness of primary attending physician for patient to participate.
Exclusion criteria
* Systolic BP \<90 mmHg on admission * Hemoglobin (Hgb) \< 8 g/dl * Known allergy or intolerance to furosemide or low dose dopamine. * Hemodynamically significant arrhythmias including ventricular tachycardia or defibrillator shock within 4 weeks * Acute coronary syndrome within 4 weeks * Cardiac diagnoses in addition to or other than HFpEF: i. Active myocarditis ii. Hypertrophic obstructive cardiomyopathy iii. Severe valvular disease iv. Restrictive or constrictive cardiomyopathy, including known amyloidosis, sarcoidosis, hemachromatosis v. Complex congenital heart disease vi. Constrictive pericarditis vii. Severe pulmonary hypertension (RVSP ≥ 60), not secondary to HFpEF * Non-cardiac pulmonary edema * Clinical evidence of digoxin toxicity * Received IV vasoactive treatment or ultra-filtration therapy for heart failure since initial presentation * Anticipated need for IV vasoactive treatment or ultra-filtration for heart failure during this hospitalization * History of temporary or permanent renal replacement therapy or ultrafiltration * History of renal artery stenosis \> 50% * Need for mechanical hemodynamic support * Sepsis * Terminal illness (other than HF) with expected survival of less than 1 year * Previous adverse reaction to the study drugs * Use of IV iodinated contrast material/dye in last 72 hours or planned during hospitalization * Enrollment or planned enrollment in another randomized clinical trial during this hospitalization * Inability to comply with planned study procedures * Pregnancy or nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Serum Creatinine at 72 Hours. | 72 hours | Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation. |
| Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic | 72 hours | Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by diuretic strategy |
| Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine | 72 hours | Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by dopamine strategy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bolus Furosemide If the patient is not on a prior diuretic dose, a standard dose of furosemide 40mg IV every 12 hrs, with total dose of 80 mg IV over 24 hrs will be initiated.
If the patient is already on a prescribed diuretic dose, their outpatient dose will be doubled and administered as the equivalent IV dose every 12 hrs. (i.e if the prescribed dose is furosemide 80mg by mouth twice daily, the inpatient treatment dose will be furosemide 80mg IV twice daily).
Furosemide | 19 |
| Continuous Infusion Furosemide If the patient is not on a prior diuretic dose, a standard dose of furosemide 80mg IV over 24 hrs, will be initiated.
If the patient is already on a prescribed diuretic dose, their outpatient dose will be doubled and administered as the equivalent IV dose continuously over 24 hrs. . (i.e. if the prescribed dose is furosemide 80mg by mouth twice daily, the inpatient treatment dose would be furosemide 160mg IV to be administered continuously over 24 hrs).
Furosemide | 23 |
| Bolus Furosemide Plus Dopamine Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion.
Furosemide
Dopamine | 24 |
| Continuous Furosemide Plus Dopamine Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion.
Furosemide
Dopamine | 24 |
| Total | 90 |
Baseline characteristics
| Characteristic | Bolus Furosemide | Continuous Infusion Furosemide | Bolus Furosemide Plus Dopamine | Continuous Furosemide Plus Dopamine | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 13 Participants | 12 Participants | 13 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 12 Participants | 11 Participants | 42 Participants |
| Age, Continuous | 68 years STANDARD_DEVIATION 13 | 63 years STANDARD_DEVIATION 10 | 66 years STANDARD_DEVIATION 15 | 67 years STANDARD_DEVIATION 13 | 66 years STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized Black | 12 participants | 14 participants | 15 participants | 15 participants | 56 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 6 participants | 9 participants | 9 participants | 9 participants | 33 participants |
| Sex: Female, Male Female | 17 Participants | 12 Participants | 17 Participants | 15 Participants | 61 Participants |
| Sex: Female, Male Male | 2 Participants | 11 Participants | 7 Participants | 9 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 19 | 3 / 22 | 4 / 23 | 3 / 22 |
| other Total, other adverse events | 0 / 19 | 0 / 22 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 19 | 0 / 22 | 0 / 23 | 0 / 22 |
Outcome results
Primary
Percent Change in Serum Creatinine at 72 Hours.
Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation.
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours. | 4 percent change in serum creatinine | Standard Deviation 22 |
| Continuous Infusion Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours. | 11 percent change in serum creatinine | Standard Deviation 21 |
| Bolus Furosemide Plus Dopamine | Percent Change in Serum Creatinine at 72 Hours. | 5 percent change in serum creatinine | Standard Deviation 17 |
| Continuous Furosemide Plus Dopamine | Percent Change in Serum Creatinine at 72 Hours. | 20 percent change in serum creatinine | Standard Deviation 28 |
Primary
Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic
Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by diuretic strategy
Time frame: 72 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bolus Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic | 4.6 percent change in serum creatinine |
| Continuous Infusion Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic | 16 percent change in serum creatinine |
p-value: 0.01895% CI: [2, 20.8]t-test, 2 sided
Primary
Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine
Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by dopamine strategy
Time frame: 72 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bolus Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine | 8.0 percent change in serum creatinine |
| Continuous Infusion Furosemide and no Dopamine | Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine | 12.8 percent change in serum creatinine |
p-value: 0.3395% CI: [-14.4, 4.9]t-test, 2 sided