Brief Title
Pressure Assessment to Improve Outcomes After TAVR: a Registry
Official Title
Pressure Assessment to Improve Outcomes After TAVR: a Registry
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.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score
Secondary Outcome
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score
Condition
Hypertension
Intervention
Eplerenone
Study Arms / Comparison Groups
Eplerenone
Description: Eplerenone 50 mg daily, administered orally for 8 weeks.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
12
Start Date
June 3, 2019
Completion Date
February 27, 2020
Primary Completion Date
February 20, 2020
Eligibility Criteria
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.
Gender
All
Ages
55 Years - 100 Years
Accepts Healthy Volunteers
No
Contacts
Anthony Bavry, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03923530
Organization ID
201901097
Responsible Party
Principal Investigator
Study Sponsor
North Florida Foundation for Research and Education
Collaborators
Malcom Randall VA Medical Center
Study Sponsor
Anthony Bavry, MD, Principal Investigator, University of Florida
Verification Date
May 2020