Medtronic CoreValve SURTAVI Trial -Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI)
SURTAVI Clinical Investigation Protocol:
Background:Purpose:The purpose of this study is to investigate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk by randomizing patients to either Surgical Aortic Valve Replacement (SAVR) or TAVI with the Medtronic CoreValve System or Medtronic EVOLUT-R system.Objectives:The primary objective of this trial is to evaluate in a prospective randomized fashion whether TAVI is non-inferior to SAVR with respect to composite endpoint of all-cause mortality and disabling stroke at 24 months in patients with symptomatic severe aortic stenosis and at intermediate surgical risk.The secondary objective of this trial is to assess differences in quality of life, clinical benefit (efficacy endpoints) and health economics in patients with symptomatic severe aortic stenosis and at intermediate risk treated with either Transcatheter Aortic Valve Implantation (TAVI) or Surgical Aortic Valve Replacement (SAVR).Study population:Patients who have symptomatic severe Aortic Stenosis at intermediate surgical risk defined by a Society of Thoracic Surgeons (STS) mortality risk of 4% and 10% will be presented to the Heart Team for inclusion in the trial.Methodology/study arms:This study is designed as a prospective, multi-center, multi-national, randomized, interventional trial to investigate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk. Approximately 1600 subjects will be recruited in up to 115 investigational centers located in the United States, Canada and Europe. The study may be expanded to include additional geographies based on enrollment rates and identification of qualified centers. Subjects will be randomized on a 1:1 basis to either transcatheter aortic valve implant (TAVI) with one of two approved valves, Medtronic CoreValve System (MCS)/EVOLUT R System or to surgical aortic valve replacement (SAVR).Primary Endpoint:All-cause mortality or disabling stroke at 24 months Follow-up: Subjects will be followed through 5 years with assessments at 30 days, 3 months, 6 months, 12 months, 18 months, 24 months, and 3, 4, and 5 years post MCS TAVI or post SAVR.Statistics/Analysis:The statistical analysis will be performed by the statistics department of Medtronic. As primary analysis all randomized subjects will be analyzed following the modified intention to treat (mITT) approach; i.e. analyses will be conducted on the cohort of subjects who undergo an attempted study treatment, analyzed according to the randomized assignment. A secondary analysis of key objectives will be performed according to the therapy actually received.
SURTAVI Single-Arm, Non-Randomized Phase (Addendum Version 1.0):
Background: The Medtronic CoreValve SURTAVI Trial is a prospective, randomized, multicenter investigational trial. The purpose of this trial is to investigate the safety and effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk by randomizing patients to either Surgical Aortic Valve Replacement (SAVR) or TAVI. The purpose of this addendum to the Medtronic CoreValve SURTAVI Trial protocol is to conclude the randomized phase and initiate the single-arm, non-randomized, TAVI only phase of the trial.
Objectives: The primary objective of this trial is to evaluate the safety and effectiveness of the Medtronic CoreValve System and CoreValve Evolut R System, as measured by a composite endpoint of all-cause mortality or disabling stroke at 24 months in patients with symptomatic severe aortic stenosis and at intermediate surgical risk.
Patient Population: Patients who have symptomatic severe Aortic Stenosis who are determined by the Heart Team to be at intermediate surgical risk.
Design: The single-arm phase is designed as a prospective, multi-center in the United States, non-randomized, interventional trial to evaluate the safety and effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe, symptomatic Aortic Stenosis (AS) at intermediate surgical risk.
All enrolled subjects will be assigned to transcatheter aortic valve implant (TAVI).
Follow-Up: All enrolled subjects will undergo in-clinic follow-up evaluations at the following time points post implant, 30 days, 6 months, 12 months, 24 months and annually thereafter through 5 years. In the single-arm phase of this trial, the 3 months and 18 months follow-up visits are no longer required like in the primary SURTAVI Trial Clinical Investigation Protocol (CIP).
Statistical Analysis: There are three analysis populations defined for this study. The primary analysis for the primary objective and most secondary objectives will use the attempted implant population. The echocardiographic assessment of valve performance data will be analyzed based on the implanted population. (1)All enrolled population all subjects who are enrolled in the trial (2) Attempted implant population - all subjects in whom a procedure is attempted. A procedure attempt is defined as when the subject is brought into the procedure room and any of the following have occurred: anesthesia administered, vascular line placed, TEE placed or any monitoring line placed. (3) Implanted population All attempted implant subjects who are actually implanted with the investigational TAVI device.
Portico Resheathable Transcatheter Aortic Valve System US IDE Trial
Rationale: To potentially offer a SJM transcatheter Portico valve that is safe and effective for subjects with symptomatic severe aortic valve stenosis who are considered at high or extreme risk for conventional surgical aortic valve replacement. Purpose: The Portico Transcatheter Heart Valve is indicated for patients with symptomatic severe native aortic stenosis, who are considered high surgical or extreme surgical risk. Study population: High-Risk:Subjects must have comorbidities such that the surgeon and cardiologist CoPIs concur that the predicted risk of operative mortality is 15% and/or a minimum STS score of 8, and has symptomatic aortic stenosis. Extreme Risk: The subject, after formal consults by a cardiologist and two cardiovascular surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement, and has symptomatic aortic stenosis. Specifically the predicted risk of operative mortality should exceed 50%. Study Methodology: The PORTICO clinical trial is a prospective, multicenter, randomized, controlled clinical study, designed to evaluate the safety and effectiveness of the SJM Portico Transcatheter Heart Valve and Delivery Systems (Portico) via the transfemoral and alternative delivery methods, in high and extreme risk cohorts. If the participant takes part in the study, their treatment will be determined in a way similar to flipping a coin, called randomization. Prior to randomization, patients will be classified as high or extreme risk and stratified by vascular access within each risk group. Depending on their valve size they will be randomized into one of two study groups which will determine the device they are implanted with: Test Group: Portico Transcatheter Heart Valve / Control Group: FDAapproved Transcatheter Valve. There are also 2 registries in this study and they may be placed in a registry which will not require randomization. All registry patients will receive a TAVI and will have follow up as a research participant. The first registry is called a rollin registry. They may be considered for this registry based on their order of enrollment in the study. If they are one of the first three patients to enroll in the trial they will not be randomized but will receive a Portico valve. The second registry is for patients who already have a prosthetic aortic valve in place and are in need of replacing the prosthetic valve. If they qualify for this registry, a Portico valve will be implanted inside their existing prosthetic valve. The PORTICO trial will include a maximum of 908 subjects at up to 70 investigational sites. Study endpoints: A non-hierarchical composite of all-cause mortality, disabling stroke, or moderate or greater aortic insufficiency/regurgitation at one year for high and extreme risk cohort. Follow-up: 30 day, 6 month, One year and annually thereafter through year 5. Statistics: Basic descriptive statistics and P values will be reported.Analysis: The primary analysis will be based on the intent to treat (ITT) population. The ITT population is defined at the time that randomization treatment is assigned to the subject. For the primary analysis in this study, subjects will be analyzed according to their ITT arm, and the randomization day will be considered Day 0 when referring to a specific number of days.
The Medtronic CoreValve Evolut R US Clinical Study
Transcatheter aortic valve implantation (TAVI) has become a routine treatment option at specialized heart centers treating patients with severe aortic stenosis who are at high risk for surgical aortic valve replacement (SAVR). Medtronic has developed modifications to the Medtronic CoreValve System Transcatheter Aortic Valve frame and delivery catheter system to enable recapture of the device before it is fully released from the delivery system. These modifications are incorporated in the CoreValve Evolut R System.
The purpose of the study is to evaluate the safety and efficacy of the CoreValve Evolut R System in patients with severe symptomatic aortic stenosis who are considered at high through extreme risk for surgical aortic valve replacement.
This is a prospective, single arm, historical controlled, multi-center study. This study will involve no more than 250 subjects in up to 25 sites. The study population includes males and females with severe symptomatic aortic stenosis who are considered at high through extreme risk for surgical aortic valve replacement. Subjects will be followed up to 5 years following implantation.
Study endpoints are safety endpoints and efficacy endpoints. Safety endpoints are: All-cause mortality rate, stroke (disabling) rate, incidence of permanent pacemaker implant rate at 30 days. Efficacy endpoints are: Device success rate, Resheath and recapture success rate, percent of subjects with mild prosthetic regurgitation at early post-implant, hemodynamic performance metrics at 30 days.
Statistics/analysis: Subjects who are taken to the procedure room for implantation will comprise the study population evaluated for the study objectives and associated endpoints. An initial analysis will be performed when both of the following conditions are met:
1. The first 150 consecutive implanted subjects have completed their 30 day follow-up.
2. A total of 25 resheath or recapture attempts inclusive of all valve sizes, have been performed.
The final analysis will be performed after a minimum of 150 subjects but no greater than 250 subjects are implanted with the study device and followed for 5 years.
All endpoints are descriptive and no statistical hypothesis test will be performed.
Medtronic CoreValve® U.S. Expanded Use Study
The primary objective of the study is to evaluate the safety and effectiveness of the
Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme
Risk Pivotal Trial population due to one or more additional co-morbidities, as measured by a
composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic
severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled
in this study have a predicted operative mortality or serious, irreversible morbidity risk
of ≥50% at 30 days associated with surgical aortic valve replacement.