The Medtronic TMVR Pilot Study
Research type
Research Study
Full title
Evaluation of the Safety and Performance of the Twelve Transcatheter Mitral Valve Replacement System in High Risk Patients with Severe Symptomatic Mitral Regurgitation
IRAS ID
187061
Contact name
Vinayak Bapat
Contact email
Sponsor organisation
Medtronic BRC
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Research Summary
The Twelve Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) System is designed for trans-apical delivery of a self-expanding bioprosthetic heart valve within the native mitral valve for treatment of mitral regurgitation (blood flows the wrong way). The study is a prospective, multi-centre, non-randomised trial to evaluate the safety and performance of the Twelve Intrepid™ TMVR System in very high risk patients with severe, symptomatic mitral regurgitation, who are deemed ineligible for conventional surgery.
This study will enroll and treat up to 20 subjects in the UK and will be performed only in highly specilised cardiac surgery centres. Treated subjects will be followed through 5 years post-implant.Summary of results
Introduction: The Intrepid™ TMVR System is an MV implant designed to treat patients with severe MR. It is designed for transapical access and delivery of a self-expanding bioprosthetic bovine pericardial valve within the native MV. The Intrepid™ TMVR implant is intended to function similar to a standard bioprosthetic valve implant, in that it allows blood to flow only in the forward direction, thereby relieving MR.
A standard valve implant, however, is sewn directly into the heart during surgery in which the chest is fully open, the patient is placed on cardiopulmonary bypass support, and the heart is temporarily stopped.
The Intrepid™ TMVR implant is placed through a less invasive minithoracotomy procedure, without requiring cardiopulmonary bypass support or stopping the heart, thereby reducing the risks associated with these more invasive procedures.
Study Purpose The purpose of the study is to evaluate the safety and performance of the Intrepid™ TMVR System in very high-risk patients with severe, symptomatic MR, who are deemed ineligible for standard surgery.
Study Objectives: The primary objective is to evaluate the safety of the Intrepid™ TMVR System. The primary endpoint is assessment of the nature, severity, and frequency of complications associated with the delivery and/or implantation of the device. The secondary objective is to evaluate the performance of the Intrepid™ TMVR System.
• The secondary endpoints include assessment of:
▪ The ability to accurately deliver and place the implant within the native anatomy ▪ The degree of improvement of MR grade and symptoms, and the durability of TMVR function ▪ The fit of the implant within the native anatomy, including fixation, sealing and compatibility with native structures Summary of Results: 95 subjects received an attempted implant procedure with the Intrepid™ TMVR System; 95.7% of these procedures were successful. There were no USADEs in the study. 70.5% of subjects experienced an implant- or delivery-related SAE through 30 days post-procedure. There There were 18 deaths within 30 days, 12 more through 1 year post-procedure, and 32 more until the end of the study.
During the acute post-operative period (until 30 days after the procedure), 24.3% of subjects had a major bleeding event, 16.2% required reoperation (14.1% because of bleeding events), 14.7% had a major cardiac structural complication, 21.5% had acute kidney injury, and 3.6% of subjects had a disabling stroke. MR was reduced to none/trace or mild in all subjects, which was sustained through 5 years post-procedure, with no clinically significant increases in MV gradient, one clinically significant LVOT obstruction during the procedure, and no clinically significant LVOT obstruction post-procedure.
Among subjects who completed the 5-year assessments, NYHA grade improved in 84.6% of subjects, and mean 6MWT increased by 28.4 meters compared to baseline. At the 1-year follow-up, the 6MWT had increased by 61.9 meters compared to baseline. Quality of life with the Minnesota Living with Heart Failure questionnaire improved for 78.3% of subjects who completed their 12-month follow-up, compared to baseline.
Study Endpoints Primary safety endpoint: • Implant- or delivery-related serious adverse events (through 30 days post-procedure). Secondary performance endpoints:
• Successful access, delivery of implant, and retrieval of the delivery system • Reduction in MR grade from baseline (measured by echo through 30 days post-procedure) • No significant MV stenosis (measured by echo through 30 days post-procedure) • Left ventricular outflow tract (LVOT) patency (measured by echo through 30 days post-procedure) • Improvement of New York Heart Association (NYHA) Class from baseline (through 30 days post-procedure) Additional exploratory endpoints: • Measured by echo post-procedure through 5 years: • Reduction in MR grade from baseline • No significant MV stenosis • LVOT outflow tract (LVOT) patency • Improvement in LVEF • Improvement in cardiac output/cardiac index • Reduction in LV end-systolic and end-diastolic dimensions • Change in 6-minute walk test (6MWT) from baseline through 5 years • Change in QOL (MLHFQ) from baseline through 12 months • Change in NYHA from baseline through 5 years • Procedural times (e.g., deployment time, apical access duration, rapid pacing duration) • Re-hospitalizations for heart failure through 5 years • MVARC1 defined outcomes of: (see Appendix 15.1.4 for specific
definitions) • Technical success Device success • Procedural success • Individual subject success Study Population The study includes subjects who require replacement of their native MV because of severe, symptomatic MR, and are at high risk and deemed ineligible for conventional MV surgery.
This final study report provides results on 95 attempted subjects at 21 sites across Europe, Australia, and the US.
Study Design The study is a prospective, multi-center, non-randomized pilot study to evaluate the safety and performance of the Intrepid™ TMVR System. The study was designed to be executed in multiple geographies (EU, AUS, USA), with identical study objectives, study procedures, follow-up, and data collection. Slight differences in inclusion/exclusion criteria based on geography-specific protocols do not change patient population (see section 16.1 for more details). Statistical Methods For the primary purposes of this pilot study, each subject’s data will be reviewed individually. Study results will be summarized using descriptive statistics. Baseline demographic and clinical variables will be summarized. Predefined statistical “success” or “pass” criteria for the Study endpoints are not applicable for this feasibility study, as it is not a powered, hypothesis-driven study. Continuous variables will be summarized with means, standard deviations, medians, interquartile ranges, minimums, and maximums. Categorical variables will be summarized with frequencies and percentages.
The sample size is based upon industry standards for pilot-stage studies of medical devices; the sample size was not statistically derived, as this is not a hypothesis-driven study.
Results: 95 subjects received an attempted implant procedure with the Intrepid™ TMVR System; 95.7% of these procedures were successful. There were no USADEs in the study. 70.5% of subjects experienced an implant- or delivery-related SAE through 30 days post-procedure. There were 18 deaths within 30 days, 12 more through 1 year post-procedure, and 32 more until the end of the study. During the acute postoperative period (until 30 days after the procedure), 24.3% of subjects had a major bleeding event, 16.2% required reoperation (14.1% because of bleeding events), 14.7% had a major cardiac structural complication, 21.5% had acute kidney injury, and 3.6% of subjects had a disabling stroke. MR was reduced to none/trace or mild in all subjects, which was sustained through 5-years post-procedure, with no clinically significant increases in MV gradient, one clinically significant LVOT obstruction during the procedure, and no clinically significant LVOT obstruction postprocedure. Among subjects who completed the 5-year assessments, NYHA grade improved in 84.6% of subjects, and mean 6MWT increased by 28.4 meters compared to baseline. At the 1-year follow-up, the 6MWT had increased by 61.9 meters compared to baseline. Quality of life with the Minnesota Living with Heart Failure questionnaire improved for 78.3% of subjects who completed their 12-month follow-up, compared to baseline.
Conclusions The Intrepid™ TMVR System consistently performs as intended, demonstrating the clinical benefits of substantial sustained reduction or elimination of MR, as well as a substantial improvement in symptoms and quality of life for subjects suffering from severe, symptomatic MR.
The Intrepid™ TMVR System has an acceptable safety profile when considered for subjects with severe symptomatic MR who are determined to be at high risk and deemed ineligible for conventional MV surgery.REC name
London - Dulwich Research Ethics Committee
REC reference
15/LO/1923
Date of REC Opinion
23 Dec 2015
REC opinion
Further Information Favourable Opinion