CoreValve® System Australia/New Zealand Clinical Study

To evaluate the performance, efficacy and safety of the percutaneous implantation of the CoreValve® prosthetic aortic valve in patients with severe symptomatic native aortic valve stenosis that have an elevated surgical risk

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: Medtronic CoreValve® System

Detailed Description

Prospective, non-randomized, single-arm multi-center trial conducted under a common protocol at 10 centers in Australia and New Zealand.

• Study Type: Interventional
• Enrollment (Actual): 634
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia
      • St. Vincents Sydney
  • Queensland
    • Chermside, Queensland, Australia
      • Prince Charles Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Hospital
    • Fitzroy, Victoria, Australia
      • St. Vincent's Melbourne
    • Melbourne, Victoria, Australia
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3004
      • Epworth Hospital
  • Western Australia
    • Perth, Western Australia, Australia
      • Royal Perth Hospital
• New Zealand
  • Auckland, New Zealand
    • Mercy Hospital
  • Hamilton, New Zealand
    • Waikato Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Documented severe aortic valve stenosis
2. Access vessel diameter >6 mm as defined pre procedure via angiographic measure
3. Aortic valve annulus diameter ≥ 20 mm and < 29 mm as defined pre procedure by echocardiographic measure
4. Ascending aorta diameter ≤ 43 mm at the sino-tubular junction

5. Native aortic valve disease, defined as valve stenosis with an aortic valve area<1cm2 (<0.6cm2 /m2) as defined pre procedure by echocardiographic measure

   AND (Assessment of Surgical Risk)

   Age ≥ 80 years

   AND/OR

   Surgical risk calculated with logistic EuroSCORE ≥ 20%,

   AND/OR

   Age ≥ 65 years with one or two (but not more than 2) of the following criteria:

   • Cirrhosis of the liver (Child class A or B)
   • Pulmonary insufficiency : VMS < 1 liter
   • Previous cardiac surgery (CABG, valvular surgery)
   • Porcelain aorta
   • Pulmonary hypertension > 60 mmHg and high probability of cardiac surgery for other than valve replacement
   • Recurrent pulmonary embolus
   • Right ventricular insufficiency
   • Thoracic burning sequelae contraindicating open chest surgery
   • History of mediastinum radiotherapy
   • Severe connective tissue disease resulting in a contraindication to surgery
   • Cachexia (clinical impression)
6. Study subjects must be willing and able to attend all follow-up visits within specified visit windows, and agree to undergo all protocol evaluations at each visit

Exclusion Criteria:

1. Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, clopidogrel, nitinol, porcine products, or contrast media which cannot be adequately pre-medicated
2. Any sepsis, including active endocarditis.
3. Recent myocardial infarction (<30 days)
4. Any left ventricular or atrial thrombus as determined pre procedure by echocardiography
5. Uncontrolled atrial fibrillation
6. Mitral or tricuspid valvular insufficiency (> grade II)
7. Previous aortic valve replacement (mechanical valve or stented bioprosthetic valve)
8. Evolutive or recent CVA (cerebrovascular accident), (<3 months)
9. Femoral, iliac or aortic vascular condition (e.g. stenosis, tortuosity), that make impossible insertion and endovascular access to the aortic valve
10. Symptomatic carotid or vertebral arteries narrowing (> 70%) disease
11. Abdominal or thoracic aortic aneurysm
12. Bleeding diathesis or coagulopathy, or patient will refuse blood transfusion
13. Evolutive disease with life expectancy less than one year
14. Creatinine clearance < 20 ml/min
15. Active gastritis or known peptic ulcer disease
16. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medtronic CoreValve® System Implantation; Patients with symptomatic severe aortic stenosis who have an elevated surgical risk	Device: Medtronic CoreValve® System; The Medtronic CoreValve® System device is designed to replace the native aortic valve without the requirement for open heart surgery and without concomitant surgical removal of the failed native valve in patients with symptomatic severe aortic stenosis who have an elevated surgical risk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) Rate	Defined as a composite of all cause death, myocardial infarction(MI) (Q-wave & non-Q-wave), stroke, and re-intervention (defined as any emergent cardiac surgery or percutaneous re-intervention catheter procedure that repairs, otherwise alters or adjusts or replaces a previously implanted valve)	30 days
Percentage of Participants With Overall Device Success	Vascular access, delivery and deployment of the device, and retrieval of the delivery system; Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function); Intended performance of the prosthetic valve (aortic valve area > 1.2 cm2 (by echocardiography using the continuity equation) and mean aortic valve gradient < 20 mmHg, without moderate or severe prosthetic valve aortic regurgitation); Only one valve implanted; No occurrence of in-hospital MACCE	24-48 hours after the procedure or before the discharge
Cardiac-related Death	Defined as all death resulting from a cardiac cause or complications of a cardiac procedure and / or death of an unknown cause; this category includes valve-related deaths and non-valve-related cardiac deaths (e.g. congestive heart failure, acute myocardial infarction, documented fatal arrhythmias).	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Mortality	is defined per Valve Academic Research Consortium-1 consensus document (VARC-1), including Cardiovascular and non-cardiovascular mortality.	30 days
Myocardial Infarction	Included Q-wave and non-Q-wave.	30 days
Stroke	Is a neurological deficit lasting more than 24 hours, or lasting 24 hours or less with a brain imaging study showing infarction.	30 days
Re-intervention	Any emergent surgical or percutaneous interventional catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve.	30 days

Collaborators and Investigators

• Sponsor: Medtronic Cardiovascular
• Collaborators: Medtronic Australasia
• Investigators: Study Director: Eric Vang, Medtronic; Principal Investigator: Ian T Meredith, MD, Monash Heart Medical Center

Publications and helpful links

General Publications

• Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. doi: 10.1016/j.jacc.2008.05.007. No abstract available.
• Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006 Dec;82(6):2111-5. doi: 10.1016/j.athoracsur.2006.07.048.
• Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A, Wenaweser P, Sauren B, Mohr FW, Walther T, Zickmann B, Iversen S, Felderhoff T, Cartier R, Bonan R. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol. 2007 Jul 3;50(1):69-76. doi: 10.1016/j.jacc.2007.04.047. Epub 2007 Jun 6.
• Sundt TM, Bailey MS, Moon MR, Mendeloff EN, Huddleston CB, Pasque MK, Barner HB, Gay WA Jr. Quality of life after aortic valve replacement at the age of >80 years. Circulation. 2000 Nov 7;102(19 Suppl 3):III70-4. doi: 10.1161/01.cir.102.suppl_3.iii-70.
• Kastrup J, Wennevold A, Thuesen L, Nielsen TT, Kassis E, Fritz-Hansen P, Thayssen P. Short- and long-term survival after aortic balloon valvuloplasty for calcified aortic stenosis in 137 elderly patients. Dan Med Bull. 1994 Jun;41(3):362-5.
• Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Sebagh L, Bash A, Nusimovici D, Litzler PY, Bessou JP, Leon MB. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol. 2004 Feb 18;43(4):698-703. doi: 10.1016/j.jacc.2003.11.026.
• Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Nercolini D, Tapiero S, Litzler PY, Bessou JP, Babaliaros V. Treatment of calcific aortic stenosis with the percutaneous heart valve: mid-term follow-up from the initial feasibility studies: the French experience. J Am Coll Cardiol. 2006 Mar 21;47(6):1214-23. doi: 10.1016/j.jacc.2006.01.049. Epub 2006 Feb 9.
• Grube E, Laborde JC, Gerckens U, Felderhoff T, Sauren B, Buellesfeld L, Mueller R, Menichelli M, Schmidt T, Zickmann B, Iversen S, Stone GW. Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation. 2006 Oct 10;114(15):1616-24. doi: 10.1161/CIRCULATIONAHA.106.639450. Epub 2006 Oct 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2008
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: November 17, 2009
• First Submitted That Met QC Criteria: November 17, 2009
• First Posted (Estimate): November 18, 2009

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Aortic Valve Stenosis; Aortic Valve Insufficiency
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: CV-PAVR-R2007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO