Mitral Valve Insufficiency
Conditions
Brief summary
PILOT: The study is a pilot trial to evaluate the safety and performance of the Twelve TMVR System in high risk mitral regurgitation patients. EFS: The study is an Early Feasibility Study to evaluate the safety and performance of the Medtronic Intrepid™ Transcatheter Mitral Valve Replacement System with Transfemoral Transseptal access in Patients with moderate-Severe or severe, Symptomatic Mitral Regurgitation
Detailed description
PILOT: The study is a prospective, multi-center, non-randomized study to evaluate the safety and performance of The Intrepid™ TMVR System in patients with severe, symptomatic mitral regurgitation, who are at high risk for conventional mitral valve surgery. EFS: The study is a multi-center, prospective, non-randomized, trial to evaluate the safety and performance of the Medtronic Intrepid™ Transcatheter Mitral Valve Replacement System with Transfemoral Transseptal access in Patients with Moderate-Severe or Severe, Symptomatic Mitral Regurgitation
Interventions
DEVICETwelve TMVR Implant
Implantation of the Twelve TMVR System - Apical
DEVICEMedtronic Intrepid™ Transcatheter Transfemoral Mitral Valve Replacement System
Implantation of the Medtronic Intrepid™ Transcatheter Mitral Valve- Transfemoral
Sponsors
Medtronic Cardiovascular
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Severe mitral regurgitation (PILOT) * moderate-severe or severe mitral regurgitation (EFS) * Symptomatic mitral regurgitation (NYHA Class II-IV) * Deemed to be at high risk for conventional mitral valve surgery by the local heart team (including, at minimum, a cardiac surgeon, interventional cardiologist, and an echocardiologist) (PILOT and EFS) * Subjects anatomically suitable for the Intrepid TMVR delivery system, including transfemoral and transseptal access (EFS only) * Native mitral valve geometry and size compatible with the Intrepid™ TMVR (PILOT) Key
Exclusion criteria
* Left ventricular ejection fraction (LVEF) \< 20 (PILOT) or \<30% (EFS) * Evidence of intracardiac mass, thrombus, or vegetation * Prior valve surgery or need for other valve surgery * Prior stroke within 30 days (PILOT) or 90 days (EFS) * Gastrointestinal bleeding within 6 months (PILOT) * Prior myocardial infarction 90 days (EFS) * Need for coronary revascularization * History of, or active, endocarditis if antibiotics are required (EFS) * Renal insufficiency; Serum Creatinine \> 2.5 mg/dL (PILOT) or Creatinine Clearance \<30 cc/min (EFS)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With Adverse Events | 30 days | PILOT: Site Reported Serious Adverse Events Implant or Delivery Related Through 30-Days EFS: Implant, Delivery or device related serious adverse events through 30 days post procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subject With Left Ventricular Outflow Tract (LVOT) Patency | 30 Days post procedure | EFS: Left Ventricular Outflow Tract (LVOT) Patency measured by echo through 30 days post-procedure |
| Number of Subjects Without Mitral Valve Stenosis | Through 30 days | PILOT: No significant mitral Valve (MV) Stenosis measured by echo through 30 days post-procedure EFS: No Significant Mitral Valve (MV) Stenosis measured by echo through 30 days post-procedure |
| Number of Subjects With Procedural Success | Procedure | PILOT: Successful access, delivery of implant, and retrieval of the delivery system EFS: Successful access, delivery of implant, and retrieval of the delivery system |
| Number of Subject With Left Ventricle Output Tract (LVOT) Patency | Through 30 days | PILOT: LVOT patency measured by echo through 30 days post-procedure. |
| Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Through 30 days | PILOT: Change in NYHA Class from Baseline through 30 days post-procedure. |
| Number of Subjects With Greater Than or Equal Moderate (2+) Mitral Regurgitation at 30-days | Through 30 days | PILOT: Number of subjects with a core lab-evaluated mitral regurgitation grade greater than or equal to moderate at 30-days |
| Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | 30 days | PILOT: Change in MR Grade from baseline measured by echo through 30 days post-procedure. Measured by Echo 30 days post procedure. |
Countries
Australia, Denmark, Finland, France, Greece, United Kingdom, United States
Participant flow
Recruitment details
Patient recruitment occurred April 2015 to March 2019 at 23 sites (12 U.S.,3 Australia, 8 Europe)(PILOT), Jan. 2020 to Aug. 2022 at 11 U.S sites (EFS). Patients with severe, symptomatic mitral regurgitation at high surgical risk (PILOT) or moderate-severe or severe, symptomatic mitral regurgitation, ineligible for conventional mitral valve surgery (EFS) were screened for eligibility, provided informed consent, met all inclusion criteria, and no exclusion criteria, were enrolled.
Pre-assignment details
These are single-arm studies. Patients who signed informed consent & fulfill inclusion criteria and none of the exclusion criteria listed below are eligible for enrollment. A Patient Review Committee (PRC) (PILOT)/ Screening Committee (EFS), which consisted of cardiac surgery, interventional cardiology, and echocardiology representatives who were not participating investigators, reviewed potential patients' clinical and imaging data to help ensure appropriate patient selection across all sites.
Participants by arm
| Arm | Count |
|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant Twelve TMVR Implant: Implantation of the Twelve TMVR System -Apical
Medtronic Intrepid™ Transcatheter Transfemoral Mitral Valve Replacement System: Implant of Intrepid valve -Transfemoral | 128 |
| Total | 128 |
Baseline characteristics
| Characteristic | Transcatheter Mitral Valve Replacement (TMVR) Implant |
|---|---|
| Age, Continuous | 74.0 years STANDARD_DEVIATION 9.2 |
| Atrial Fibrillation | 15 Participants |
| Creatinine Clearance | 61.4 cc/min STANDARD_DEVIATION 25.7 |
| EUROSCORE II (%) | 8.0 % risk of mortality STANDARD_DEVIATION 6.7 |
| Mitral Valve Etiology Primary | 20 Participants |
| Mitral Valve Etiology Secondary | 74 Participants |
| NYHA Class NYHA I | 0.0 Participants |
| NYHA Class NYHA II | 11 Participants |
| NYHA Class NYHA III | 71 Participants |
| NYHA Class NYHA IV | 13 Participants |
| NYHA Class NYHA l | 0 Participants |
| NYHA Class NYHA ll | 10 Participants |
| NYHA Class NYHA lll | 22 Participants |
| NYHA Class NYHA lV | 1 Participants |
| Previous Cardiovascular Surgery | 45 Participants |
| Previous Myocardial infarction | 40 Participants |
| Race/Ethnicity, Customized Asian | 2 Paticipants |
| Race/Ethnicity, Customized Black or African American | 9 Paticipants |
| Race/Ethnicity, Customized Caucasian | 81 Paticipants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Paticipants |
| Race/Ethnicity, Customized RAC and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment Australia | 19 Participants |
| Region of Enrollment Denmark | 2 Participants |
| Region of Enrollment Finland | 1 Participants |
| Region of Enrollment France | 9 Participants |
| Region of Enrollment Greece | 3 Participants |
| Region of Enrollment United Kingdom | 9 Participants |
| Region of Enrollment United States | 52 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 54 Participants |
| STS Score- PROM (MV Replacement only) | 5.3 % risk of mortality STANDARD_DEVIATION 2.8 |
| STS Score - PROM (MV Replacement Only) | 6.5 % risk of mortality STANDARD_DEVIATION 4.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 62 / 95 | 7 / 33 |
| other Total, other adverse events | 88 / 95 | 33 / 33 |
| serious Total, serious adverse events | 93 / 95 | 32 / 33 |
Outcome results
Primary
Percent of Subjects With Adverse Events
PILOT: Site Reported Serious Adverse Events Implant or Delivery Related Through 30-Days EFS: Implant, Delivery or device related serious adverse events through 30 days post procedure
Time frame: 30 days
Population: PILOT: 95 participants EFS: 33 participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Percent of Subjects With Adverse Events | PILOT | 67 % of subjects with Event |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Percent of Subjects With Adverse Events | EFS Implant or Delivery Related | 72.7 % of subjects with Event |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Percent of Subjects With Adverse Events | EFS Device Related | 36.4 % of subjects with Event |
Secondary
Change in Mitral Regurgitation (MR) From Baseline Through 30 Days
PILOT: Change in MR Grade from baseline measured by echo through 30 days post-procedure. Measured by Echo 30 days post procedure.
Time frame: 30 days
Population: Number of subjects with evaluable baseline and 30 day CoreLab echo MR grading.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | PILOT: Improved | 71 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | PILOT: No change | 0 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | PILOT: Worsened | 0 Participants |
Secondary
Change in Mitral Regurgitation (MR) From Baseline Through 30 Days
EFS: Change in MR Grade from Baseline measured by echo through 30 days post-procedure. Measured by Echo 30 days post procedure.
Time frame: Through 30 Days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | Improved | 30 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | No change | 0 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in Mitral Regurgitation (MR) From Baseline Through 30 Days | Worsened | 0 Participants |
Secondary
Change in New York Heart Association (NYHA) From Baseline Through 30 Days
EFS: Change in NYHA Class from Baseline through 30 days post procedure
Time frame: Through 30 Days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Improved | 21 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | No Change | 6 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Worsened | 3 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Died Prior to Visit | 0 Participants |
Secondary
Change in New York Heart Association (NYHA) From Baseline Through 30 Days
PILOT: Change in NYHA Class from Baseline through 30 days post-procedure.
Time frame: Through 30 days
Population: PILOT: Number of subjects with evaluable baseline and 30 days NYHA classification.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Improved | 54 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | No change | 20 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Worsened | 1 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Change in New York Heart Association (NYHA) From Baseline Through 30 Days | Died Prior to Visit | 18 Participants |
Secondary
Number of Subjects With Greater Than or Equal Moderate (2+) Mitral Regurgitation at 30-days
PILOT: Number of subjects with a core lab-evaluated mitral regurgitation grade greater than or equal to moderate at 30-days
Time frame: Through 30 days
Population: Number of subjects with a core lab-evaluated mitral regurgitation grade greater than or equal to moderate at 30-days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects With Greater Than or Equal Moderate (2+) Mitral Regurgitation at 30-days | 0 Participants |
Secondary
Number of Subjects Without Mitral Valve Stenosis
PILOT: No significant mitral Valve (MV) Stenosis measured by echo through 30 days post-procedure EFS: No Significant Mitral Valve (MV) Stenosis measured by echo through 30 days post-procedure
Time frame: Through 30 days
Population: PILOT: N= 62. Number of subjects with evaluable baseline and 30 day CoreLab echoes for MV stenosis; defined as an MV mean gradient \< 5 mmHg and effective orifice area (EOA) ≥ 1.5 cm² based on echocardiography core lab data.~EFS: N=25. Number of subjects with EOA \>= 1.5 cm2, Transmitral Gradient \<5 mmHg, PVL \<=Mild, and No Hemolysis with PVL
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects Without Mitral Valve Stenosis | PILOT | 19 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects Without Mitral Valve Stenosis | EFS | 11 Participants |
Secondary
Number of Subjects With Procedural Success
PILOT: Successful access, delivery of implant, and retrieval of the delivery system EFS: Successful access, delivery of implant, and retrieval of the delivery system
Time frame: Procedure
Population: PILOT: One subject had their procedure aborted prior to delivery catheter insertion and was thus excluded from deployment and retrieval denominator
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects With Procedural Success | PILOT: Successful access | 94 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects With Procedural Success | PILOT: Successful Delivery of implant | 90 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects With Procedural Success | PILOT: Successful retrieval of the delivery system | 94 Participants |
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subjects With Procedural Success | EFS: Procedural Success (Number of Patients with Successful TMVR Placement) | 31 Participants |
Secondary
Number of Subject With Left Ventricle Output Tract (LVOT) Patency
PILOT: LVOT patency measured by echo through 30 days post-procedure.
Time frame: Through 30 days
Population: Number of subjects with evaluable baseline and 30 day CoreLab echoes for LVOT patency.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Number of Subject With Left Ventricle Output Tract (LVOT) Patency | 62 Participants |
Secondary
Percent of Subject With Left Ventricular Outflow Tract (LVOT) Patency
EFS: Left Ventricular Outflow Tract (LVOT) Patency measured by echo through 30 days post-procedure
Time frame: 30 Days post procedure
Population: Number of subjects with evaluable baseline and 30 day CoreLab echoes for LVOT patency.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Transcatheter Mitral Valve Replacement (TMVR) Implant | Percent of Subject With Left Ventricular Outflow Tract (LVOT) Patency | 100 Percent |