Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction

NCT ID: NCT01901809

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2018-05-31

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.

Conditions

Heart Failure, Diastolic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Bolus furosemide and no dopamine

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).

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

Continuous infusion furosemide and no dopamine

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).

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

Bolus furosemide plus dopamine

Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

Dopamine

Intervention Type: DRUG

Continuous furosemide plus dopamine

Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

Dopamine

Intervention Type: DRUG

Interventions

Furosemide

Intervention Type: DRUG

Dopamine

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kavita Kavita, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins School of Medicine

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38775253 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30098962 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA 00083629

Identifier Type: -

Identifier Source: org_study_id