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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Johns Hopkins University
Sponsor:
Information provided by (Responsible Party):
Stuart D. Russell, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01901809
First received: May 15, 2013
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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. We 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 GFR. Secondary endpoints for readmission, functional capacity, quality of life, and amount of diuresis will also be collected.


Condition Intervention Phase
Heart Failure, Diastolic
Drug: Furosemide
Drug: Dopamine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Evaluation of HFpEF Patients With Acute Heart Failure and Dopamine (ROPA-DOP) Trial

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Change in glomerular filtration rate at 72 hours [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Change in glomerular filtration rate (GFR, mL/min/1.73 m2) as calculated by the Modification of Diet in Renal Disease (MDRD) study formula from randomization to 72 hrs from treatment protocol initiation.


Secondary Outcome Measures:
  • Change in incidence of acute kidney injury [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    Change in incidence of acute kidney injury (defined as rise in in-hospital serum creatinine of > 0.3 mg/dL and relative increase of > 25% of the serum creatinine) from randomization to 72 hrs.

  • Volume of diuresis measured in liters [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Volume of diuresis measured in liters calculated as both cumulative volume of diuresis measured in liters and cumulative volume of diuresis measured in liters adjusted for BMI

  • Six minute walk distance [ Time Frame: Basline, 72 hours, and on the day of discharge, an expected average of 6 days. ] [ Designated as safety issue: No ]
    Change in distance during 6 minute walk test from admission to 72 hrs and on the day of discharge, an expected average of 6 days.

  • Global well-being assessment score [ Time Frame: Baseline, 72 hours, and and on the day of discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
    Global well-being assessment score from admission to 72 hrs, and on the day of hospital discharge, an expected average of 6 days. To be assessed by a Visual Analog Scale (VAS).

  • Heart failure readmissions [ Time Frame: 30 day and 6 months ] [ Designated as safety issue: No ]
    24. 30 day and 6 month hospital readmission or ER visit for major adverse cardiovascular event, heart failure, renal failure, syncope, or arrhythmia. Readmission events will be adjudicated by a Clinical Event Committee consisting of 2-3 cardiologists not directly in contact with patients enrolled in the study.

  • Frailty index [ Time Frame: Baseline, 72 hours, and and on the day of discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
    Change in frailty index from admission to 72 hrs, and on the day of hospital discharge, an expected average of 6 days. To be assessed by the Johns Hopkins Older Americans Independence Center Online Frailty Assessment Tool

  • Subjective dyspnea score [ Time Frame: Baseline, 72 hours, and on the day of discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
    Subjective dyspnea score from admission to 72 hrs, and on the day of hospital discharge, an expected average of 6 days. To be assessed by a Visual Analog Scale (VAS).

  • Length of stay [ Time Frame: Length in days from admission to discharge from the hospital, an expected average of 6 days. ] [ Designated as safety issue: No ]
    Length of stay of hospitalization in days, an expected average of 6 days


Estimated Enrollment: 120
Study Start Date: August 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Admission to Johns Hopkins Hospital for acute decompensated heart failure.
  2. Patient ≥18 years of age
  3. Estimated GFR of > 15 milliliters/min/1.73m2 determined by the MDRD equation
  4. Willingness to provide informed consent
  5. 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.
  6. Negative pregnancy test in a female of child bearing potential
  7. Willingness of primary attending physician for patient to participate.

Exclusion Criteria:

  1. Systolic BP <90 mmHg on admission
  2. Hemoglobin (Hgb) < 8 g/dl
  3. Known allergy or intolerance to furosemide or low dose dopamine.
  4. Hemodynamically significant arrhythmias including ventricular tachycardia or defibrillator shock within 4 weeks
  5. Acute coronary syndrome within 4 weeks
  6. 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

  7. Non-cardiac pulmonary edema
  8. Clinical evidence of digoxin toxicity
  9. Received IV vasoactive treatment or ultra-filtration therapy for heart failure since initial presentation
  10. Anticipated need for IV vasoactive treatment or ultra-filtration for heart failure during this hospitalization
  11. History of temporary or permanent renal replacement therapy or ultrafiltration
  12. History of renal artery stenosis > 50%
  13. Need for mechanical hemodynamic support
  14. Sepsis
  15. Terminal illness (other than HF) with expected survival of less than 1 year
  16. Previous adverse reaction to the study drugs
  17. Use of IV iodinated contrast material/dye in last 72 hours or planned during hospitalization
  18. Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
  19. Inability to comply with planned study procedures
  20. Pregnancy or nursing mothers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01901809

Contacts
Contact: Stuart D Russell, MD 410-955-5708 srusse14@jhmi.edu
Contact: Kavita Sharma, MD 410-955-5708 ksharma8@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Stuart D Russell, MD    410-955-5708    srusse14@jhmi.edu   
Contact: Kavita Sharma, MD    410-955-5708    ksharma8@jhmi.edu   
Principal Investigator: Stuart D Russell, MD         
Sub-Investigator: Kavita Sharma, MD         
Sub-Investigator: Steven Schulman, MD         
Sub-Investigator: David Thiemann, MD         
Sub-Investigator: Robert Weiss, MD         
Sub-Investigator: David Kass, MD         
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Stuart D Russell, MD Johns Hopkins School of Medicine
  More Information

No publications provided

Responsible Party: Stuart D. Russell, Chief of Heart Failure and Transplant, Associate Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01901809     History of Changes
Other Study ID Numbers: JHH HFpEF 1
Study First Received: May 15, 2013
Last Updated: April 17, 2014
Health Authority: United States: Institutional Review Board

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
Dopamine Agents
Diuretics
Furosemide
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Natriuretic Agents
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators

ClinicalTrials.gov processed this record on September 18, 2014