Pressure Assessment to Improve Outcomes After TAVR: a Registry

NCT03923530 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 201901097
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

TAVR; KCCQ; Aortic stenosis; Diastolic dysfunction; Invasive hemodynamic assessment

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 8 weeks

Secondary Outcomes (6)

• Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score

  Baseline, 8 weeks

• Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score

  Baseline, 8 weeks

• Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score

  Baseline, 8 weeks

• Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score

  Baseline, 8 weeks

• Systolic Blood Pressure

  Baseline, 8 weeks

Study Arms (1)

Eplerenone

EXPERIMENTAL

Eplerenone 50 mg daily, administered orally for 8 weeks.

Drug: Eplerenone

Interventions

Eplerenone DRUG

Eplerenone 50 mg daily

Also known as: Inspra

Eplerenone

Eligibility Criteria

• Age: 55 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Malcom Randall VA Medical Center

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Hypertension; Aortic Valve, Calcification of; Aortic Valve Stenosis

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Anthony Bavry
• Organization: NF South Ga VAMC

anthony.bavry@va.gov

352-548-4726

Study Officials

• Anthony Bavry, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Cardiovascular Catheterization Laboratory

Model Details: Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 22, 2019
• Study Start: June 3, 2019
• Primary Completion: February 20, 2020
• Study Completion: February 27, 2020
• Last Updated: May 28, 2020
• Results First Posted: May 28, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)