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Pressure Assessment to Improve Outcomes After TAVR: a Registry

Primary Purpose

Hypertension, Aortic Stenosis, Calcific, Quality of Life

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Eplerenone
Sponsored by
North Florida Foundation for Research and Education
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring TAVR, KCCQ, Aortic stenosis, Diastolic dysfunction, Invasive hemodynamic assessment

Eligibility Criteria

55 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  1. Enroll 10 subjects with hypertension and abnormal hemodynamics after TAVR.

  2. This is a greater than minimal risk study.

    1. 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.

    2. 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.

  3. 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.

    a. 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%).

  4. Monitoring.

    a. 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.

  5. 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.

Sites / Locations

  • Malcom Randall VA Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eplerenone

Arm Description

Eplerenone 50 mg daily, administered orally for 8 weeks.

Outcomes

Primary Outcome Measures

Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score
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

Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score
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.
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score
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.
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score
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.
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score
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.
Systolic Blood Pressure
Cuff systolic blood pressure
Diastolic Blood Pressure
Cuff diastolic blood pressure

Full Information

First Posted
April 18, 2019
Last Updated
May 14, 2020
Sponsor
North Florida Foundation for Research and Education
Collaborators
Malcom Randall VA Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03923530
Brief Title
Pressure Assessment to Improve Outcomes After TAVR: a Registry
Official Title
Pressure Assessment to Improve Outcomes After TAVR: a Registry
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
June 3, 2019 (Actual)
Primary Completion Date
February 20, 2020 (Actual)
Study Completion Date
February 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
North Florida Foundation for Research and Education
Collaborators
Malcom Randall VA Medical Center

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Aortic Stenosis, Calcific, Quality of Life, Heart Failure With Preserved Ejection Fraction
Keywords
TAVR, KCCQ, Aortic stenosis, Diastolic dysfunction, Invasive hemodynamic assessment

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eplerenone
Arm Type
Experimental
Arm Description
Eplerenone 50 mg daily, administered orally for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Eplerenone
Other Intervention Name(s)
Inspra
Intervention Description
Eplerenone 50 mg daily
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
Title
Systolic Blood Pressure
Description
Cuff systolic blood pressure
Time Frame
Baseline, 8 weeks
Title
Diastolic Blood Pressure
Description
Cuff diastolic blood pressure
Time Frame
Baseline, 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Enroll 10 subjects with hypertension and abnormal hemodynamics after TAVR. This is a greater than minimal risk study. 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. 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. 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. a. 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%). Monitoring. a. 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Bavry, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Malcom Randall VA Medical Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Pressure Assessment to Improve Outcomes After TAVR: a Registry

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