Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction

NCT01901809 | Completed Phase 4 Results DMC

• 1 other identifier: NA 00083629
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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

Keywords

Heart failure, diastolic; HFpEF; Diuretics; Dopamine

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (4)

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).

Drug: Furosemide

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).

Drug: Furosemide

Bolus furosemide plus dopamine

ACTIVE COMPARATOR

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

Drug: Furosemide; Drug: Dopamine

Continuous furosemide plus dopamine

ACTIVE COMPARATOR

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

Drug: Furosemide; Drug: Dopamine

Interventions

Furosemide DRUG

Bolus furosemide and no dopamine; Bolus furosemide plus dopamine; Continuous furosemide plus dopamine; Continuous infusion furosemide and no dopamine

Dopamine DRUG

Bolus furosemide plus dopamine; Continuous furosemide plus dopamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Negative pregnancy test in a female of child bearing potential
• Willingness of primary attending physician for patient to participate.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (2)

• 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.

  PMID: 38775253 DERIVED

• 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.

  PMID: 30098962 DERIVED

MeSH Terms

Conditions

Heart Failure, Diastolic

Interventions

Furosemide; Dopamine

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

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.

Results Point of Contact

• Title: Kavita Sharma, MD
• Organization: Johns Hopkins University School of Medicine

ksharma8@jhmi.edu

410-955-7670

Study Officials

• Kavita Kavita, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: July 17, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2017
• Study Completion: May 1, 2018
• Last Updated: August 16, 2018
• Results First Posted: May 17, 2018

Record last verified: 2018-07

Locations

US (1)