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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bolus furosemide and no dopamine | Active Comparator | 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). |
|
| Continuous infusion furosemide and no dopamine | Active Comparator | 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). |
|
| Bolus furosemide plus dopamine | Active Comparator | Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min |
|
| Continuous furosemide plus dopamine | Active Comparator | Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Furosemide | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Serum Creatinine at 72 Hours. | Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation. | 72 hours |
| 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 | 72 hours |
| 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 | 72 hours |
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Inclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Kavita Kavita, MD | Johns Hopkins School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38775253 | Derived | Rasoul D, Zhang J, Farnell E, Tsangarides AA, Chong SC, Fernando R, Zhou C, Ihsan M, Ahmed S, Lwin TS, Bateman J, Hill RA, Lip GY, Sankaranarayanan R. Continuous infusion versus bolus injection of loop diuretics for acute heart failure. Cochrane Database Syst Rev. 2024 May 22;5(5):CD014811. doi: 10.1002/14651858.CD014811.pub2. | |
| 30098962 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Serum Creatinine at 72 Hours. | Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation. | Posted | Mean | Standard Deviation | percent change in serum creatinine | 72 hours |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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Early termination leading to small numbers of subjects analyzed. The investigator team was blinded to study assignment; however, the patient and treating physicians were un-blinded.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kavita Sharma, MD | Johns Hopkins University School of Medicine | 410-955-7670 | ksharma8@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 8, 2013 | Apr 17, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D054144 | Heart Failure, Diastolic |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D005665 | Furosemide |
| D004298 | Dopamine |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Dopamine | Drug |
|
| Sharma K, Vaishnav J, Kalathiya R, Hu JR, Miller J, Shah N, Hill T, Sharp M, Tsao A, Alexander KM, Gupta R, Montemayor K, Kovell L, Chasler JE, Lee YJ, Fine DM, Kass DA, Weiss RG, Thiemann DR, Ndumele CE, Schulman SP, Russell SD; Osler Medical Housestaff. Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine: The ROPA-DOP Trial. JACC Heart Fail. 2018 Oct;6(10):859-870. doi: 10.1016/j.jchf.2018.04.008. Epub 2018 Aug 8. |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
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 |
| OG002 | Bolus Furosemide Plus Dopamine | Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min Furosemide Dopamine |
| OG003 | Continuous Furosemide Plus Dopamine | Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min Furosemide Dopamine |
|
|
| 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 | Posted | Mean | 95% Confidence Interval | percent change in serum creatinine | 72 hours |
|
|
|
|
| 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 | Posted | Mean | 95% Confidence Interval | percent change in serum creatinine | 72 hours |
|
|
|
|
| 5 |
| 19 |
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | 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 | 3 | 22 | 0 | 22 | 0 | 22 |
| EG002 | 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 | 4 | 23 | 0 | 23 | 0 | 23 |
| EG003 | 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 | 3 | 22 | 0 | 22 | 0 | 23 |
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| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |