Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction

Phase 4

Completed

Conditions: Heart Failure, Diastolic

Interventions: Drug: Furosemide
Drug: Dopamine

Registration Number: NCT01901809

Lead Sponsor: Johns Hopkins University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Continuous furosemide plus dopamine	Furosemide	Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min
Bolus furosemide plus dopamine	Furosemide	Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min
Bolus furosemide and no dopamine	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).
Continuous infusion furosemide and no dopamine	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).
Bolus furosemide plus dopamine	Dopamine	Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min
Continuous furosemide plus dopamine	Dopamine	Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min

Primary Outcome Measures

Name	Time	Method
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
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.	72 hours	Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation.