Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05603026 |
| Other study ID # |
STUDY20200834 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 21, 2023 |
| Est. completion date |
December 30, 2024 |
Study information
| Verified date |
November 2023 |
| Source |
University Hospitals Cleveland Medical Center |
| Contact |
Luis Dallan, MD |
| Phone |
216-844-1000 |
| Email |
luisdallan[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The hypothesis is that SEV result in superior valvular hemodynamics (more pronounced during
exercise) and exercise capacity relative to BEV. Furthermore, the hypothesis is that stress
CMR will be able to demonstrate differences in these hemodynamic parameters. CMR will also
provide refined assessment of paravalvular leak and its impact on ventricular function and on
clinical outcomes.
Description:
Project Overview/Summary Transcatheter aortic valve replacement (TAVR) is an alternative to
open heart surgery for the treatment of severe aortic stenosis, and has recently been
approved for low surgical risk patients. This has resulted in a shifting of TAVR patient
demographics to younger and more active individuals. It is, therefore, imperative to deliver
excellent hemodynamics after valve replacement to enable patients to recover an active
lifestyle with enhanced exercise capacity. Several studies, mostly conducted with resting
echocardiogram have suggested self-expanding valves (SEV) Evolut R, Evolut PRO, Evolut PRO+
(Medtronic , Minneapolis, MN) are associated with favorable hemodynamics, which may allow for
improved exercise capacity in active patients.
Currently, there are different TAVR valves are commercially available in the United States.
The Sapien 3 valve (Edwards Lifesciences, Irvine, CA) is an annular, balloon expandable valve
(BEV) and the Evolut PRO+ valve features a supra-annular design and is a SEV. A recent study
utilizing resting echocardiogram demonstrated better hemodynamics of supra-annular SEV
compared with BEV, mostly in patients with smaller annuli.
Cardiac magnetic resonance (CMR) has emerged as an important tool in the non-invasive
assessment of patients with valvular heart disease. While CMR has been used for the diagnosis
and quantification of valvular heart disease, there is a paucity of data on its use for the
assessment of valvular hemodynamics in the post TAVR setting. Furthermore, it would be of
utmost importance to understand how these devices perform during exertion. Of note, cardiac
magnetic resonance techniques permit quantification of the myocardial extracellular volume
fraction (ECV), representing a surrogate marker of reactive interstitial fibrosis, and late
gadolinium enhancement (LGE), representing replacement fibrosis or scar. ECV and LGE have
been independently linked with heart failure (HF) events.
Several studies have demonstrated that non-invasive CMR can be used to calculate non-invasive
pressure-volume loops using cine imaging and non-invasive brachial blood pressure. This
enables assessment of myocardial performance beyond LVEF. CMR-derived myocardial stroke work
is a novel method allowing non-invasive assessment of total active myocardial performance,
including both constructive and wasted myocardial work. Specifically, changes in LV stroke
work have been shown to carry important prognostic information following TAVR.
Hypothesis The hypothesis is that SEV result in superior valvular hemodynamics (more
pronounced during exercise) and exercise capacity relative to BEV. Furthermore, the
hypothesis is that stress CMR will be able to demonstrate differences in these hemodynamic
parameters. CMR will also provide refined assessment of paravalvular leak and its impact on
ventricular function and on clinical outcomes.
STUDY DESIGN
Study Population There will be enrolled prospectively and retrospectively patients who have
undergone TAVR at University Hospitals Cleveland Medical Center with different commercially
available transcatheter valves and different sizes. It will then be screened all patients
undergoing TAVR for a total of 90 patients.
All patients referred for TAVR will be considered for enrollment provided they meet the
following inclusion and exclusion criteria. Inclusion criteria include all of the following:
1) Aortic valve stenosis with clinical indication for valve replacement decided by a
dedicated heart team; 2) Planned transfemoral TAVR; 3) 18 years of age or older; 4) Able to
give informed consent.
Exclusion criteria will include: 1) Patients with permanent pacemakers or implantable
defibrillators; 2) Patients with non-MRI safe implants; 3) Severe claustrophobia; 4)
Inability or contraindication to perform exercise bike stress test; 5) Arrhythmia which would
prevent adequate cardiac gating, including atrial fibrillation; 6) Reduced left ventricular
systolic function (<40%); 7) History of surgical aortic valve replacement or patients who
undergo a valve-in-valve TAVR procedures; 8) Significant non-treated coronary artery disease.
Primary and Secondary Outcomes The co-primary endpoints will be analysed at 1-year follow up
and will consist in: change in effective orifice area (EOA), mean gradient and peak gradient
over time between valve types; and left ventricular stroke work.
Secondary outcomes will include: myocardial fibrosis; myocardial extra-cellular volume
fraction; ability to perform stress CMR studies in post TAVR patient population, exercise
capacity post TAVR, echocardiographic measures of valve and heart function, standard clinical
outcomes of morbidity and mortality associated with TAVR.
Patient Enrollment, Treatment, and Follow-up Patients will be screened for
inclusion/exclusion criteria as part of their pre-TAVR clinical evaluation. We will screen
all patients undergoing TAVR for a total of 90 patients. There will be enrolled 45 patients
to undergo TAVR and receive Sapien 3 BEV with two sizes (23 mm and 26 mm) and 45 patients to
undergo TAVR with Evolut FX SEV in two available sizes (26 mm and 29 mm). All patients will
be required to sign an informed consent. The choice for TAVR valve will be at the operator's
discretion. Patients will be seen at 7- and 30-days post TAVR per routine clinical practice.
Baseline clinical parameters, procedural variables and the occurrence of MACE and bleeding
events will be determined by history and corroborated by examining relevant medical records.
Transthoracic echocardiography will be performed immediately post TAVR, 1-day post TAVR and
again at 30-days post TAVR as per standard clinical protocol. Patients will be treated with
aspirin 81 mg daily and clopidogrel 75 mg daily for a minimum of 3 months, followed by
aspirin 81 mg daily indefinitely thereafter.
MRI Imaging Protocol The first CMR will be performed up to three months prior to the TAVR
procedure. Secondly, a stress CMR study will be performed 30-days (up to three months) post
TAVR. Patients will have their EOA, valvular regurgitation, LV function, mean pressure
gradient and peak pressure gradient assessed by standard MRI protocols. Patients will undergo
an exercise stress MRI to assess exercise capacity, valve hemodynamics under stress and
differences in hemodynamics between valve types. Finally, a follow up CMR will be performed
1-year after the TAVR, where it will be evaluated myocardial extracellular volume fraction
and replacement fibrosis/scar in addition to the variables previously described.
CMR-Derived Non-invasive LV Pressure-Volume Loops It will be the able to calculate
non-invasive pressure-volume loops using cine imaging and non-invasive brachial blood
pressure. LVPV loops are derived non-invasively with ventricular-volume, heart rate and
brachial pressure as inputs. LV stroke work is derived from the area of the generated
pressure-volume loop.
MRI Stress Protocol The exercise MRI test will be performed on an MRI-compatible supine cycle
ergometer that will be attached to the end of the MRI bed. Patients will be positioned on the
gentry with a molding pad placed beneath them to help maintain patient position on the table
during exercise for pre- and post-exercise scans. After initial imaging, the patient will
remain supine on the table to complete the symptom-limited exercise stress test. Heart rate
and blood pressure will be monitored continuously throughout exercise and during
post-exercise scans. Immediately post-exercise, the patient will be placed back in the
scanner for post-exercise.
Patient Safety Patients will be monitored for adverse events (AE) and serious adverse events
(SAE). A data safety and monitoring board will be appointed to oversee and adjudicate these
events. An AE is the development of an undesirable medical condition or the deterioration of
a pre-existing medical condition following or during exposure to a pharmaceutical product,
whether or not considered causally related to the product. Patients undergoing MRI and stress
CMR will be screened for relevant contraindications by the research team at the time of their
scan. SAE is an AE that results in death, requires in-patient hospitalization or prolongation
of existing hospitalization, results in persistent or significant disability, results in a
congenital abnormality or birth defect, or is an important medical event that may jeopardize
the subject or may require medical intervention to prevent one of the outcomes listed above.
The causality of SAEs (their relationship to all study treatments) will be assessed by the
investigators. The following variables will be collected for each AE: 1) Type of AE, 2) Date
and time when the AE started and stopped, 3) Whether the AE is serious or not, 4)
Investigator causality rating against the investigational product, 5) Action taken with
regard to investigational product, 6) Whether AE caused subject's withdrawal from the study,
7) Outcome. The following variables will be collected for each SAE: 1) Date AE met criteria
for serious AE, 2) Date Investigator became aware of serious AE, 3) Reason AE is serious, 4)
Date of hospitalization if applicable, 5) Date of discharge, if applicable, 6) Probable cause
of death, if applicable, 7) Date of death, if applicable, 8) Autopsy performed, if
applicable, 9) Causality assessment in relation to Study procedure(s), 10) Causality
assessment in relation to other medication, 11) Description of AE.
Risks:
The only foreseeable risk of this study are:
1. Breach of confidentiality, which will be avoided by de-identifying patient data by name,
and strictly guarding all data collected for the completion of the study.
2. Issues related to stress MRI: complications related to stress MRI, such as adverse
reactions to drugs (ex. gadolinium), imaging features (ex. claustrophobia) or issues
related to the stress induction (ex. fatigue, cardiac impairment) may occur, but will be
explained prior to the image acquisition.
Benefits:
Through registry based analysis it will be isolated clinical determinants of morbidity and
mortality, as well as the best clinical and procedural outcomes, which will inform best
practices for TAVR procedures.
Statistical Analysis:
Continuous variables will be reported as median (interquartile range) and categorical
variables as number (percentage). Cumulative survival free from outcomes will be assessed by
Kaplan-Meier (KM) curves and Cox proportional hazard ratios will be calculated to create
predictive and association models for the outcomes of interest. P-values of ≤0.05 will be
considered statistically significant. Statistical analyses will be done using SAS, version
9.3 (SAS Institute, Cary, NC).
Data Safety Monitoring Plan:
The Principal Investigator will ensure that all the data is securely collected and stored in
a password protected REDCap database. Each patient reviewed will be de-identified by a
specific study number and names and MR numbers will not be used in the final statistical
analysis. It will be ensured that after statistical analysis there is no means of connecting
any patient reviewed to specific data associated with that patient.
