The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Edwards Lifesciences
Sponsor:
Information provided by (Responsible Party):
Edwards Lifesciences
ClinicalTrials.gov Identifier:
NCT01314313
First received: March 7, 2011
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

The purpose of this trial is to determine the safety and effectiveness of the Edwards SAPIEN XT and the Edwards SAPIEN 3 transcatheter heart valve and delivery systems which are intended for use in patients with symptomatic, calcific, severe aortic stenosis.


Condition Intervention Phase
Symptomatic Severe Aortic Stenosis
Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The PARTNER II Trial "Placement of AoRTic TraNscathetER" Valves Trial" (US) [Edwards Study 2010-12]

Resource links provided by NLM:


Further study details as provided by Edwards Lifesciences:

Primary Outcome Measures:
  • Cohort A: Non-hierarchical composite of death and disabling stroke [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
  • Cohort B: Non-hierarchical composite of death (all cause), disabling stroke and repeat hospitalization [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
  • PIIS3 High Risk Cohort/NR7: Non-hierarchical composite event of death, all stroke, and aortic insufficiency. [ Time Frame: Effectiveness time frame 1 year and safety 30 days ] [ Designated as safety issue: Yes ]
    PIIS3 High Risk Cohort: Non-inferiority analysis to historical control.

  • PIIS3 Intermediate Risk Cohort/NR8: Non-hierarchical composite endpoints of death and all stroke (effectiveness) and death, all stroke, major bleeding and major vascular complications (safety) [ Time Frame: Effectiveness time frame 1 year and safety 30 days ] ] [ Designated as safety issue: Yes ]
    PIIS3 intermediate risk cohort: Non-inferiority analysis to historical controls.

  • NR1,NR3-NR6: Freedom from mortality at 1 year. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • NR2: Freedom from mortality, major vascular complications and major bleeding. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 5550
Study Start Date: March 2011
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAPIEN XT™ valve with the NovaFlex or NovaFlex+ delivery syst Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
Operable: SAPIEN XT™ vs. AVR; Inoperable: SAPIEN XT™ vs. SAPIEN®
Experimental: SAPIEN XT™ valve with the Ascendra2 and Ascendra+ Delivery Sys Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
Operable: SAPIEN XT ™vs. AVR
Active Comparator: SAPIEN® valve with the RetroFlex3™ delivery system Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
Inoperable: SAPIEN XT™ vs. SAPIEN®
Active Comparator: AVR with a surgical bioprosthetic heart valve Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
Operable: SAPIEN XT™ vs. AVR
Experimental: SAPIEN 3™valve with the Commander Delivery System Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
High risk: SAPIEN 3™ vs. historical control; Intermediate risk: SAPIEN 3™ vs. historical control
Experimental: SAPIEN 3™ valve with the Certitude Delivery System Device: TAVR Implantation of the Transcatheter Aortic Valve Prosthesis
High risk: SAPIEN 3™ vs. historical control Intermediate risk: SAPIEN 3™ vs. historical control

Detailed Description:

A prospective multi-center trial of patients undergoing aortic valve replacement for severe aortic stenosis. Patient cohorts will include the following groups based on operative risk for surgical aortic valve replacement: inoperable, high surgical risk (STS ≥ 8%), and intermediate risk (STS = 4-8%).

The Edwards SAPIEN XT transcatheter heart valve (THV) system will be studied in patients deemed inoperable or intermediate risk. A subset of inoperable patients will be randomized to receive transcatheter aortic valve replacement (TAVR) with either the SAPIEN XT THV or the SAPIEN THV. The SAPIEN XT will be studied in intermediate risk patients randomized to receive TAVR with the SAPIEN XT or surgical AVR.

The Edwards SAPIEN 3 THV will be studied in a non-randomized fashion in patients from all three risk groups.

Data will be collected from all patients for up to five years following the valve replacement procedure.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

All Candidates for this study (Cohorts A, B and S3) must meet the following criteria:

  1. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient >40 mmHg or jet velocity greater than 4.0 m/s and an initial aortic valve area (AVA) of ≤0.8 cm2 or indexed EOA < 0.5 cm2/m2 Qualifying echo must be within 60 days of the date of the procedure.
  2. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater.
  3. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.
  4. The study patient or the study patient's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
  5. The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up.

Once eligibility in accordance to the above criteria is established, patients are assessed for operability (in-operable, high risk, intermediate risk). All candidates must meet the above criteria in order to be stratified into Cohort A, Cohort B or S3.

Additional Eligibility Criteria Specific to Cohort A:

Inclusion Criteria:

  1. STS ≥ 4
  2. Heart team (including examining cardiac surgeon) agrees on eligibility including assessment that TAVR or AVR is appropriate
  3. Heart team agrees (a priori) on treatment strategy for concomitant coronary disease (if present)
  4. Study patient agrees to undergo surgical aortic valve replacement (AVR) - if randomized to control treatment

Additional Eligibility Criteria Specific to Cohort B

Inclusion Criteria:

  1. The heart team agrees that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the probability of death or serious, irreversible morbidity is ≥ 50%.
  2. The heart team agrees the patient is likely to benefit from valve replacement.

Additional Eligibility Criteria Specific to the PIIS3 High Risk Cohort/ NR7

Inclusion Criteria:

  1. STS > 8
  2. For inoperable patients: Same as #1 for additional eligibility criteria specific to Cohort B
  3. Aortic valve annulus area range (273mm2-680 mm2) per 3D imaging (echo, CT or MRI).

Additional Eligibility Criteria Specific to the PIIS3 Intermediate Risk Cohort/ NR8

Inclusion Criteria:

  1. Assessment of Intermediate surgical risk define as STS 4-8% or Heart Team assessment of intermediate risk factors.
  2. Aortic valve annulus area range (273 mm2-680 mm2) per 3D imaging (echo, CT, or MRI).
  3. Heart team agrees (a priori) on treatment strategy for concomitant coronary disease (if present).

Exclusion Criteria

Exclusion Criteria for Cohort A, Cohort B and the S3 Cohorts (including NR7 and NR8):

  1. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)].
  2. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified.
  3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+).
  4. Preexisting mechanical or bioprosthetic valve in any position (NR3).
  5. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker or ICD (S3 Cohort only) is not excluded.
  6. Any patient with a balloon valvuloplasty (BAV) within 30 days of the procedure (unless BAV is a bridge to procedure after a qualifying ECHO).
  7. Patient with planned concomitant surgical or transcatheter ablation for Atrial Fibrillation.
  8. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Pit < 50,000 cell/mL).
  9. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
  10. Severe ventricular dysfunction with LVEF < 20%.
  11. Echocardiographic evidence of intracardiac mass, thrombus, or vegetation.
  12. Active upper GI bleeding within 3 months (90 days) prior to procedure.
  13. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
  14. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure.
  15. Renal insufficiency (creatinine> 3.0 mg/dL) and/or renal replacement therapy at the time of screening.
  16. Estimated life expectancy < 24 months (730 days) due carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
  17. Expectation that patient will not improve despite treatment of aortic stenosis.
  18. Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
  19. It is known that the patient is currently enrolled in The PARTNER I Trial.
  20. Active bacterial endocarditis within 6 months (180 days) of procedure.

Exclusion Criteria Specific to Cohort A:

  1. Heart team assessment of inoperability (including examining cardiac surgeon).
  2. Complex coronary artery disease:

    • Unprotected left main coronary artery
    • Syntax score> 32 (in the absence of prior revascularization)
  3. Native aortic annulus size < 18 mm or> 27 mm as measured by echocardiogram.
  4. Patient refuses aortic valve replacement surgery.

Exclusion Criteria Specific to Cohort B and the S3 Cohorts (including NR7 and NR8):

  1. Heart team assessment of inoperability (including examining cardiac surgeon). PIIS3 intermediate risk cohort and NR8 only.
  2. Untreated clinically significant coronary artery disease requiring revascularization. Cohort B,PIIS3 high risk cohort and NR7 only.
  3. Complex coronary artery disease (S3i and NR8 only):

    1. Unprotected left main coronary artery
    2. Syntax score > 32 (in the absence of prior revascularization)
  4. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation.
  5. Need for emergency surgery for any reason.
  6. Native aortic annulus size < 18 mm or > 25 mm for Cohort B and <16mm or >28mm for the S3 Cohort (including NR7 and NR8), as measured by echocardiogram.
  7. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma [especially if thick (> 5 mm), protruding or ulcerated] or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe "unfolding" and tortuosity of the thoracic aorta (Transfemoral).
  8. Iliofemoral vessel characteristics that would preclude safe placement of 22F or 24F for Cohort B and 14F or 16F for the S3 Cohorts (including NR7/NR8) introducer sheath such as severe obstructive calcification. Severe tortuosity or minimum average vessel size less than 7 mm (5.5 mm S3 Cohorts and NR7/NR) (Transfemoral).

Specific Criteria for Registry 1 (NR1) and Registry 4 (NR4)

Inclusion: Same criteria as Cohort B Including non-femoral access. Exclusion: Same criteria as Cohort B except exclusionary criteria #15 only excludes patients with renal insufficiency (creatinine >3.0 mg/dL).

Specific Criteria for Registry 2 (NR2)

Inclusion: Same criteria as Cohort B Including non-femoral access Exclusion: Same criteria as Cohort B, except for exclusion 22 which is modified for NR2 as follows:

• Iliofemoral vessel characteristics that would preclude safe placement of 22F or 24F introducer sheath such as severe obstructive calcification, severe tortuosity or minimum average vessel size less than 6 mm and exclusionary criteria #15 only excludes patients with renal insufficiency (creatinine> 3.0 mg/dL).

Specific Criteria for Registry 3 (NR3)

Inclusion:

  1. Stenosed or insufficient surgically implanted bioprosthetic valve in the aortic position.
  2. NYHA class > II.
  3. Heart team consensus that the risk of surgical mortality or major morbidity ≥ 50%.

Exclusion:

  1. Bioprosthetic valve labeled external diameter < 21mm.
  2. Surgical or transcatheter valve in another position on the same side of the heart (mitral and tricuspid rings are not an exclusion).
  3. Hemodynamic instability defined as requiring inotropic, pressor, or mechanical support.
  4. Infectious endocarditis within 6 months.
  5. Bacteremia within 1 month.
  6. Intra-cardiac thrombus or vegetation.
  7. Acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)].
  8. Percutaneous coronary intervention or implantation of a permanent pacemaker within 7 days of the index procedure.
  9. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), thrombocytopenia (Plt < 50,000 cell/mL).
  10. Hypertrophic cardiomyopathy with obstruction (HOCM).
  11. Severe ventricular dysfunction with LVEF < 20%.
  12. Active upper GI bleeding within 3 months (90 days) prior to procedure requiring transfusion.
  13. Inability to be anticoagulated for the study procedure.
  14. Stroke or transient ischemic attack within 6 months (180 days).
  15. Insufficiency (creatinine > 3.0 mg/dL).
  16. Estimated life expectancy < 24 months.
  17. Participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
  18. The patient requires emergency surgery for any reason.
  19. Xenograft or THV in another position.
  20. Index valve has moderate or severe paravalvular regurgitation.
  21. Index valve is unstable or rocking.
  22. Extensive, severe non-revascularized coronary disease.
  23. Increased risk of coronary obstruction by prosthetic leaflets (non-stented or internally stented valve which might extend above a coronary ostium).
  24. Increased risk of embolization (non-stented and non-calcified valve). Specific Criteria for Registry 5 (NR5) and Registry 6 (NR6) Inclusion: Same criteria as Cohort B including non-femoral access Exclusion: Same criteria as Cohort B except "Native aortic annulus size <18mm or >27mm as measured by echocardiogram and exclusionary criteria #15 only excludes patients with renal insufficiency (creatinine> 3.0 mg/dL).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01314313

Contacts
Contact: Becky Inderbitzen 949-250-6420 becky_inderbitzen@edwards.com

  Show 60 Study Locations
Sponsors and Collaborators
Edwards Lifesciences
Investigators
Principal Investigator: Martin B Leon, MD Columbia University
Principal Investigator: Craig Smith, MD Columbia University
  More Information

No publications provided

Responsible Party: Edwards Lifesciences
ClinicalTrials.gov Identifier: NCT01314313     History of Changes
Other Study ID Numbers: 2010-12
Study First Received: March 7, 2011
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Edwards Lifesciences:
SAPIEN XT
SAPIEN 3
Transfemoral
Transapical
Transaortic
NovaFlex
TAVI
Aortic Stenosis
THV
Aortic Valve
Transcatheter Heart Valve
tAVR

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on August 27, 2014