Pressure Assessment to Improve Outcomes After TAVR: a Registry

NCT ID: NCT03923530

Last Updated: 2020-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-03
• Study Completion Date: 2020-02-27

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.

Conditions

Hypertension; Aortic Stenosis, Calcific; Quality of Life; Heart Failure With Preserved Ejection Fraction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eplerenone

Eplerenone 50 mg daily, administered orally for 8 weeks.

Group Type: EXPERIMENTAL

Eplerenone

Intervention Type: DRUG

Eplerenone 50 mg daily

Interventions

Eplerenone

Eplerenone 50 mg daily

Intervention Type: DRUG

Other Intervention Names

Inspra

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Malcom Randall VA Medical Center

FED

Sponsor Role: collaborator

North Florida Foundation for Research and Education

OTHER

Sponsor Role: lead

Responsible Party

Anthony Bavry

Director of Cardiovascular Catheterization Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anthony Bavry, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Malcom Randall VA Medical Center

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

201901097

Identifier Type: -

Identifier Source: org_study_id