Early Phase 1
N=12
Pressure Assessment to Improve Outcomes After TAVR: a Registry
Hypertension · Aortic Stenosis, Calcific · Quality of Life · Heart Failure With Preserved Ejection Fraction
Bottom Line
View on ClinicalTrials.gov: NCT03923530 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
May 2020
Primary outcome: Primary: Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score — 59.4; 74.1 score on a scale — p=0.12
Study Design & Population
- Study type
- Interventional
- Phase
- Early Phase 1
- Interventions
- Eplerenone (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- North Florida Foundation for Research and Education
- Primary completion
- Feb 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score |
59.4; 74.1 | 0.12 |
| SECONDARY Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score |
53.0; 61.5 | 0.49 |
| SECONDARY Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score |
63.5; 81.5 | 0.03 sig |
| SECONDARY Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score |
54.9; 73.6 | 0.27 |
| SECONDARY Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score |
65.6; 80.1 | 0.18 |
| SECONDARY Systolic Blood Pressure |
122.5; 120.0 | 0.8 |
| SECONDARY Diastolic Blood Pressure |
56.2; 55.0 | 0.76 |
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.
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 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.
Data sourced from ClinicalTrials.gov (NCT03923530). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.