Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP)

• ClinicalTrials.gov Identifier: NCT01901809
• Recruitment Status: Completed
• First Posted: July 17, 2013
• Results First Posted: May 17, 2018
• Last Update Posted: August 16, 2018
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure, Diastolic	Drug: Furosemide; Drug: Dopamine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Evaluation of Heart Failure With Preserved Ejection Fraction (HFpEF) Patients With Acute Heart Failure and Dopamine (ROPA-DOP) Trial
• Actual Study Start Date: August 2013
• Actual Primary Completion Date: June 2017
• Actual Study Completion Date: May 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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).	Drug: Furosemide
Active Comparator: 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).	Drug: Furosemide
Active Comparator: Bolus furosemide plus dopamine; Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min	Drug: Furosemide; Drug: Dopamine
Active Comparator: Continuous furosemide plus dopamine; Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min	Drug: Furosemide; Drug: Dopamine

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Serum Creatinine at 72 Hours. [ Time Frame: 72 hours ]
   Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation.
2. Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic [ Time Frame: 72 hours ]
   Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by diuretic strategy
3. Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine [ Time Frame: 72 hours ]
   Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by dopamine strategy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Kavita Kavita, MD; Johns Hopkins School of Medicine

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] August 8, 2013

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01901809
• Other Study ID Numbers: NA 00083629
• First Posted: July 17, 2013
• Results First Posted: May 17, 2018
• Last Update Posted: August 16, 2018
• Last Verified: July 2018

Keywords provided by Johns Hopkins University:

Heart failure, diastolic; HFpEF; Diuretics; Dopamine

Additional relevant MeSH terms:

Heart Failure; Heart Failure, Diastolic; Heart Diseases; Cardiovascular Diseases; Dopamine; Furosemide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cardiotonic Agents; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Dopamine Agents; Neurotransmitter Agents; Protective Agents