Pressure Assessment to Improve Outcomes After TAVR: a Registry

• Sponsor: North Florida Foundation for Research and Education (Other)
• Overall Status: Completed
• CT.gov ID: NCT03923530
• Collaborator: Malcom Randall VA Medical Center (U.S. Fed)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 8.8
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

At the Malcom Randall Veterans Affairs Medical Center (MRVAMC), invasive cardiac pressures are routinely recorded after transcatheter aortic valve replacement (TAVR) procedures. Our research has disclosed that patients with abnormal hemodynamics (narrow aortic to ventricular end-diastolic pressure difference, indexed to heart rate) suffer from high long-term mortality, compared with patients with normal hemodynamics.This hemodynamic value can be referred to as the aortoventricular index (AVi). Hypertension and diastolic dysfunction are highly co-morbid conditions among these patients. The selective aldosterone receptor antagonist eplerenone (Inspra) is approved for use in the treatment of hypertension. Research also supports that eplerenone may be able to improve diastolic function.

This prospective study is interested in determining 1) the tolerability of eplerenone, and 2) feasibility of administering the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) among subject with abnormal cardiac hemodynamics after TAVR. This study will set the stage for a pilot randomized trial to evaluate eplerenone versus placebo among patients with abnormal hemodynamics after TAVR.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Aortic Stenosis, Calcific; Quality of Life; Heart Failure With Preserved Ejection Fraction	Drug: Eplerenone	Early Phase 1

Detailed Description

Our research has disclosed that patients who have abnormal invasive cardiac hemodynamics (narrow aortic to ventricular end-diastolic pressure difference, indexed to heart rate) after TAVR suffer from poor long-term survival. This hemodynamic value can be referred to as the aortoventricular index (AVi). In a single center observational study, the 2-year mortality rate for patient with a value ≥0.6 mm Hg/bpm was 25% compared with 36% for patients with a value <0.6 mm Hg/bpm. An abnormal AVi was an independent predictor for poor survival. Hypertension and diastolic dysfunction are 2 highly co-morbid conditions among these patients. Currently, there is lack of appreciation that pressure measurements obtained at the time of TAVR can provide long-term prognostic value. There is also a lack of understanding on how to improve outcomes and quality of life among such patients.

Eplerenone is a selective aldosterone receptor antagonist approved for use for treatment of hypertension. Animal studies have shown that aldosterone receptor antagonists can decrease interstitial myocardial fibrosis. The non-selective aldosterone receptor antagonist, spironolactone 25 mg daily compared with placebo was shown to improve diastolic function, as assessed by echocardiography, among 28 elderly subjects. A meta-analysis of eleven studies in 942 subjects found that aldosterone receptor antagonists improve diastolic function and markers of cardiac fibrosis without significant changes to left ventricular mass or dimensions. In a randomized controlled trial, eplerenone was found to be safely tolerated among asymptomatic patients with moderate to severe aortic stenosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pressure Assessment to Improve Outcomes After TAVR: a Registry
• Actual Study Start Date: Jun 3, 2019
• Actual Primary Completion Date: Feb 20, 2020
• Actual Study Completion Date: Feb 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eplerenone Eplerenone 50 mg daily, administered orally for 8 weeks.	Drug: Eplerenone; Eplerenone 50 mg daily; Other Names: Inspra

Outcome Measures

Primary Outcome Measures

1. Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score [Baseline, 8 weeks]

   The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.

Secondary Outcome Measures

1. Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score [Baseline, 8 weeks]

   The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.

2. Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score [Baseline, 8 weeks]

   The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.

3. Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score [Baseline, 8 weeks]

   The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.

4. Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score [Baseline, 8 weeks]

   The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.

5. Systolic Blood Pressure [Baseline, 8 weeks]

   Cuff systolic blood pressure

6. Diastolic Blood Pressure [Baseline, 8 weeks]

   Cuff diastolic blood pressure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

1. Enroll 10 subjects with hypertension and abnormal hemodynamics after TAVR.

2. This is a greater than minimal risk study.

3. Inclusion criteria:

• TAVR procedure performed at the Malcom Randall VA Medical Center within the last 2 years.

• Intracardiac pressures recorded 5 to 10 minutes after TAVR and AVi < 0.6 mm Hg/bpm.

• History of hypertension, taking anti-hypertensive medications, or recent systolic blood pressure ≥130 mm Hg.

1. Exclusion criteria:

• Serum potassium >5.5 mEq/L at initiation.

• Concomitant administration of strong CYP3A inhibitor (i.e. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir).

• Type 2 diabetes with microalbuminuria.

• Serum creatinine >2.0 for men and >1.8 for women.

• Creatinine clearance <50 cc/min.

• Concomitant administration of potassium supplements or potassium-sparing diuretics.

1. Subjects who are eligible to participate and signed an informed consent will be given eplerenone 50 mg daily. Study drug (eplerenone) will be paid by the North Florida Foundation for Research and Education for the duration of the study.

1. Down-titration or termination of non-essential anti-hypertensive agents is permissible so that eplerenone does not result in hypotension. Essential medications are as follows:

• Angiotensin converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers, if intolerant to ACE-inhibitors are indicated for treatment left ventricular dysfunction (i.e. left ventricular ejection fraction ≤40%), diabetes, and proteinuric chronic kidney disease.

• Beta-blockers are indicated 3 years after an acute myocardial infarction, unless there is persistent left ventricular dysfunction (i.e. left ventricular ejection fraction ≤40%).

1. Monitoring.

1. Serum potassium within the last 30 days is required before initiating eplerenone. Repeat blood draw is required within the first week, and one month after the start of treatment with eplerenone.

1. Quality of life questionnaire. a. The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) will be administered at baseline and 8 weeks. The KCCQ-12 instrument will be mailed to the subject. Study coordinator will call the subject at 8 weeks to confirm vital status, assess if any adverse reactions from eplerenone, and provide assistance to completing the KCCQ-12, if needed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Malcom Randall VA Medical Center	Gainesville	Florida	United States	32608

Sponsors and Collaborators

• North Florida Foundation for Research and Education
• Malcom Randall VA Medical Center

Investigators

• Principal Investigator: Anthony Bavry, MD, University of Florida

Study Documents (Full-Text)

• Informed Consent Form - Nov 5, 2019
• Study Protocol - Feb 27, 2020
• Statistical Analysis Plan - May 14, 2020

More Information

Publications

None provided.

• Responsible Party: Anthony Bavry, Director of Cardiovascular Catheterization Laboratory, North Florida Foundation for Research and Education
• ClinicalTrials.gov Identifier: NCT03923530
• Other Study ID Numbers: 201901097
• First Posted: Apr 22, 2019
• Last Update Posted: May 28, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Anthony Bavry, Director of Cardiovascular Catheterization Laboratory, North Florida Foundation for Research and Education: TAVR; KCCQ; Aortic stenosis; Diastolic dysfunction; Invasive hemodynamic assessment
• Additional relevant MeSH terms: Aortic Valve Stenosis; Eplerenone

Study Results

Participant Flow

Recruitment Details	Recruitment at Malcom Randall VA Medical Center

Arm/Group Title	Eplerenone
Arm/Group Description	All subjects will receive eplerenone 50 mg daily. The Kansas City Cardiomyopathy Questionnaire-12 will be administered at baseline and 8 weeks. Serum potassium within the last 30 days is required before initiating eplerenone, repeat blood draw within the first week of starting eplerenone and at 4 weeks.
Period Title: Overall Study
STARTED	12
COMPLETED	8
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Eplerenone
Arm/Group Description	All subjects will receive study drug daily. Eplerenone: 50mg daily Kansas City Cardiomyopathy Questionnaire: administered at baseline and 8 weeks Serum potassium: within the last 30 days is required before initiating eplerenone, repeat blood draw within the first week and starting eplerenone and 4 weeks after starting eplerenone
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.1 (8.6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score
Description	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	59.4 (19.7)
8 weeks	74.1 (20.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score
Description	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	53.0 (21.4)
8 weeks	61.5 (14.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score
Description	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	63.5 (20.7)
8 weeks	81.5 (14.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score
Description	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	54.9 (40.5)
8 weeks	73.6 (30.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score
Description	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	65.6 (32.2)
8 weeks	80.1 (26.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Systolic Blood Pressure
Description	Cuff systolic blood pressure
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	122.5 (16.5)
8 weeks	120.0 (26.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Diastolic Blood Pressure
Description	Cuff diastolic blood pressure
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
Measure Participants	8
Baseline	56.2 (7.7)
8 weeks	55.0 (6.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eplerenone
	Comments	Change from baseline to 8 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Eplerenone
Arm/Group Description	Eplerenone 50 mg daily administered orally to subjects
All Cause Mortality
	Eplerenone
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Eplerenone
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Eplerenone
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

[Not Specified]

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.