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

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01901809
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arms: 4
• Actual Duration (Months): 57
• Patients Per Site Per Month: 1.6

Study Details

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
• 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: Aug 1, 2013
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: May 1, 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. [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 [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 [72 hours]

   Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by dopamine strategy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Aug 8, 2013

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01901809
• Other Study ID Numbers: NA 00083629
• First Posted: Jul 17, 2013
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Johns Hopkins University: Heart failure, diastolic; HFpEF; Diuretics; Dopamine
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Diastolic; Dopamine; Furosemide

Study Results

Participant Flow

Arm/Group Title	Bolus Furosemide	Continuous Infusion Furosemide	Bolus Furosemide Plus Dopamine	Continuous Furosemide Plus Dopamine
Arm/Group Description	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). 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). Furosemide	Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine	Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine
Period Title: Overall Study
STARTED	19	23	24	24
COMPLETED	19	23	21	22
NOT COMPLETED	0	0	3	2

Baseline Characteristics

Arm/Group Title	Bolus Furosemide	Continuous Infusion Furosemide	Bolus Furosemide Plus Dopamine	Continuous Furosemide Plus Dopamine	Total
Arm/Group Description	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). 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). Furosemide	Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine	Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine	Total of all reporting groups
Overall Participants	19	23	24	24	90
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 47.4%	10 43.5%	12 50%	11 45.8%	42 46.7%
>=65 years	10 52.6%	13 56.5%	12 50%	13 54.2%	48 53.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68 (13)	63 (10)	66 (15)	67 (13)	66 (13)
Sex: Female, Male (Count of Participants)
Female	17 89.5%	12 52.2%	17 70.8%	15 62.5%	61 67.8%
Male	2 10.5%	11 47.8%	7 29.2%	9 37.5%	29 32.2%
Race/Ethnicity, Customized (participants) [Number]
Black	12 63.2%	14 60.9%	15 62.5%	15 62.5%	56 62.2%
White	6 31.6%	9 39.1%	9 37.5%	9 37.5%	33 36.7%
Other	1 5.3%	0 0%	0 0%	0 0%	1 1.1%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Serum Creatinine at 72 Hours.
Description	Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bolus Furosemide and no Dopamine	Continuous Infusion Furosemide and no Dopamine	Bolus Furosemide Plus Dopamine	Continuous Furosemide Plus Dopamine
Arm/Group Description	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). 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). Furosemide	Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min Furosemide Dopamine	Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min Furosemide Dopamine
Measure Participants	19	23	24	24
Mean (Standard Deviation) [percent change in serum creatinine]	4 (22)	11 (21)	5 (17)	20 (28)

2. Primary Outcome

Title	Percent Change in Serum Creatinine at 72 Hours - Continuous vs Intermittent Diuretic
Description	Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by diuretic strategy
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bolus Furosemide	Continuous Infusion Furosemide
Arm/Group Description	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).	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).
Measure Participants	43	47
Mean (95% Confidence Interval) [percent change in serum creatinine]	4.6	16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bolus Furosemide and no Dopamine, Continuous Infusion Furosemide and no Dopamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; 2.0 to 20.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.7
	Estimation Comments

3. Primary Outcome

Title	Percent Change in Serum Creatinine at 72 Hours - Dopamine vs No Dopamine
Description	Percent change in serum creatinine from randomization to 72 hrs from treatment protocol initiation by dopamine strategy
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dopamine	No Dopamine
Arm/Group Description	Diuretic therapy plus addition of dopamine at 3 µg/kg/min administered as an infusion.	Diuretic therapy only
Measure Participants	48	42
Mean (95% Confidence Interval) [percent change in serum creatinine]	8.0	12.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bolus Furosemide and no Dopamine, Continuous Infusion Furosemide and no Dopamine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -14.4 to 4.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.8
	Estimation Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	Bolus Furosemide		Continuous Infusion Furosemide		Bolus Furosemide Plus Dopamine		Continuous Furosemide Plus Dopamine
Arm/Group Description	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). 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). Furosemide		Intermittent furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine		Continuous furosemide diuretic therapy as outlined with the addition of dopamine at 3 µg/kg/min administered as an infusion. Furosemide Dopamine
All Cause Mortality
	Bolus Furosemide		Continuous Infusion Furosemide		Bolus Furosemide Plus Dopamine		Continuous Furosemide Plus Dopamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/19 (26.3%)		3/22 (13.6%)		4/23 (17.4%)		3/22 (13.6%)
Serious Adverse Events
	Bolus Furosemide		Continuous Infusion Furosemide		Bolus Furosemide Plus Dopamine		Continuous Furosemide Plus Dopamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/22 (0%)		0/23 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Bolus Furosemide		Continuous Infusion Furosemide		Bolus Furosemide Plus Dopamine		Continuous Furosemide Plus Dopamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/22 (0%)		0/23 (0%)		0/23 (0%)

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.