HypertensionEarly Phase 1NCT03923530
Pressure Assessment to Improve Outcomes After TAVR: a Registry
A Early Phase 1 study testing Eplerenone in people with Hypertension and Aortic Stenosis, Calcific, run by North Florida Foundation for Research and Education at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 to 100 years
- Conditions the study is for
- Hypertension, Aortic Stenosis, Calcific, Quality of Life
- What is being tested?
- Eplerenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jun 2019to 27 Feb 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
- 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Malcom Randall VA Medical Center
Gainesville, Florida, 32608
About this study
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.
Read the 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
- Being tested
- Eplerenone
- Keywords
- TAVR, KCCQ, Aortic stenosis, Diastolic dysfunction, Invasive hemodynamic assessment
- Medical subject headings
- Hypertension, Aortic Valve, Calcification of, Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra
Eplerenone 50 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Eplerenone | Experimental | Eplerenone 50 mg daily, administered orally for 8 weeks. Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 8 weeks
Secondary outcomes (6)
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.
Measured: Baseline, 8 weeks
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.
Measured: Baseline, 8 weeks
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.
Measured: Baseline, 8 weeks
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.
Measured: Baseline, 8 weeks
Systolic Blood Pressure
Cuff systolic blood pressure
Measured: Baseline, 8 weeks
Diastolic Blood Pressure
Cuff diastolic blood pressure
Measured: Baseline, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2019
- Study start3 Jun 2019
- Primary completion20 Feb 2020
- Study completion27 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- North Florida Foundation for Research and Education
- Sponsor type
- University, hospital or other
- Collaborators
- Malcom Randall VA Medical Center
- Responsible party
- Principal investigator, Anthony Bavry, North Florida Foundation for Research and Education
- Investigators
- Anthony Bavry, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03923530
- Sponsor's protocol ID
- 201901097
- Status last verified
- May 2020
- First submitted
- 18 Apr 2019
- Last updated
- 28 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pressure Assessment to Improve Outcomes After TAVR: a Registry
- ClinicalTrials.gov ID
- NCT03923530
- Acronym / sponsor ID
- 201901097
- Conditions
- Hypertension, Aortic Stenosis, Calcific, Quality of Life, Heart Failure With Preserved Ejection Fraction
- Keywords
- TAVR, KCCQ, Aortic stenosis, Diastolic dysfunction, Invasive hemodynamic assessment
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- North Florida Foundation for Research and EducationUniversity, hospital or other
- Collaborators
- Malcom Randall VA Medical Center
- Study start
- 3 Jun 2019 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 27 Feb 2020 (actual)
- First posted
- 22 Apr 2019 (actual)
- Results
- Posted 28 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.
| Arm | Type | Receives |
|---|---|---|
| Eplerenone | Experimental | Drug: EplerenoneEplerenone 50 mg daily, administered orally for 8 weeks. |
Who may qualify
- Ages
- 55 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EplerenoneAlso: InspraEplerenone 50 mg daily | Drug | Eplerenone |
Primary outcome
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score
Time frame: Baseline, 8 weeks
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.
6 secondary outcomes
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score
Time frame: Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score
Time frame: Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score
Time frame: Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score
Time frame: Baseline, 8 weeks
Systolic Blood Pressure
Time frame: Baseline, 8 weeks
Diastolic Blood Pressure
Time frame: Baseline, 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Bavry, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Eplerenone in people with Hypertension and Aortic Stenosis, Calcific, run by North Florida Foundation for Research and Education at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score (time frame: Baseline, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.