The Nordic Aortic Valve Intervention Trial (NOTION)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Odense University Hospital
Sahlgrenska University Hospital, Sweden
Danish Heart Foundation
Copenhagen Trial Unit, Center for Clinical Intervention Research
Information provided by (Responsible Party):
Daniel Steinbruchel, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01057173
First received: January 26, 2010
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

A randomized clinical trial of transcatheter aortic valve implantation (TAVI) versus conventional surgical aortic valve replacement (SAVR) in patients older than 70 years of age suffering from severe aortic valve stenosis.

Study hypothesis: TAVI will reduce post-interventional morbidity and mortality compared to SAVR.


Condition Intervention Phase
Critical Aortic Stenosis
Procedure: Transcatheter Aortic Valve Implantation
Procedure: Surgical Aortic Valve Replacement
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Transcatheter Versus Surgical Aortic Valve Implantation in Patients With Severe Aortic Valve Stenosis

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Combined rate of death from any cause, myocardial infarction, and stroke [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Outcome measures will be defined as suggested by the Valvular Academic Research Consortium (VARC)


Secondary Outcome Measures:
  • Procedural complications [ Time Frame: Within first 30 days ] [ Designated as safety issue: Yes ]
  • Admission lengths (ICU and interventional center) [ Time Frame: Within first 30 days ] [ Designated as safety issue: Yes ]
  • Combined rate of noncardiac and cardiac death, prosthesis reintervention, cardiac-, cerebral-, renal-, and pulmonary complications [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Functional status (NYHA-classification) and Quality of Life (SF-36) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Echocardiographic prosthesis and ventricular structural and functional status [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 280
Study Start Date: December 2009
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transcatheter Aortic Valve Implantation Procedure: Transcatheter Aortic Valve Implantation
Retrograde trans-femoral or trans-subclavian aortic valve implantation with the Medtronic CoreValve System(TM) bio-prosthesis (third generation system, 18 Fr, CE mark approved)
Other Name: TAVI
Active Comparator: Surgical Aortic Valve Replacement Procedure: Surgical Aortic Valve Replacement
Conventional surgical aortic valve replacement with a bio-prosthesis using normothermic cardiopulmonary bypass and cold blood cardioplegia cardiac arrest
Other Name: SAVR

Detailed Description:

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a new and rapidly evolving treatment option for patients with severe degenerative aortic valve stenosis. Short- and mid-term results with transcatheter valve prostheses are promising in high-risk surgical patients, but long-term results are lacking. TAVI could potentially be an attractive minimally invasive treatment also for patients with moderate and low surgical risk, but no comparison has been made with the standard surgical treatment for aortic valve stenosis.

AIM: To compare TAVI and surgical aortic valve replacement (SAVR) in patients with severe aortic valve stenosis.

POPULATION: All patients with severe degenerative aortic valve stenosis referred for elective or subacute aortic valve intervention will be screened for study eligibility. To be included subjects must be 70 years or older, anatomical and technical eligible for both interventions, expected to survive more than 1 year after the intervention, and able to provide written informed consent. Study exclusion criteria include isolated aortic valve regurgitation or other significant valve disease, coronary artery disease requiring revascularisation at the time of referral, previous open heart surgery, a myocardial infarction or percutaneous coronary intervention within the last year, a cerebral infarction within the previous 30 days, severe renal -, pulmonary -, or infectious disease, and unstable preoperative condition.

DESIGN: The project is a national multicenter randomized clinical trial. Patients fulfilling all inclusion- and no exclusion criteria will be randomized to either TAVI or SAVR. Randomization will be 1:1 with 140 subjects in each group and stratified according to centre, age (70-74 years vs 75 and older), and coronary co-morbidity not requiring revascularisation (yes vs no). Primary outcome will be assessed by a blinded adjudication committee. Patients screened but not included in the study will be followed yearly. Screening and inclusion will commence in December 2009. Inclusion is expected to last 2 to 3 years, and subjects will be followed for 5 years.

INTERVENTIONS: Subjects randomized to TAVI will undergo percutaneous retrograde trans-femoral or trans-subclavian aortic valve implantation with the Medtronic CoreValve(TM) self-expandable bio-prosthesis. Before implantation a balloon dilatation of the aortic annulus will be performed. Subjects randomized to SAVR will undergo conventional surgical aortic valve replacement with a bio-prosthesis on cardiopulmonary bypass in normothermia with cold cardioplegia cardiac arrest. All interventions will be performed under general anaesthesia, and post-interventional medical and anticoagulation treatment will be uniform.

END POINTS: The primary end point is a combined outcome measure consisting of death from any cause, myocardial infarction, and stroke one year after the intervention. Secondary end points are death from any cause, cardiac death, cardiac -, cerebral -, pulmonary -, and renal complications, prosthesis re-intervention, procedure success and - time, admission lengths, functional class, quality of life, prosthesis and left ventricular structure and function. Follow-up visits will be performed after 30 days, 3, 6 and 12 months, and yearly thereafter for a minimum of 5 years.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have severe degenerative aortic valve stenosis (echocardiographic criteria: AV effective orifice area (EOA) of < 1 cm2, mean AV gradient of > 40 mmHg, or AV peak systolic velocity of > 4.0 m/s)
  • Patients must be symptomatic from the aortic valve stenosis (dyspnoea in NYHA-class II or greater, angina pectoris, or syncope), or asymptomatic but with echocardiographic evidence of left ventricular hypertrophy, decreased left ventricular ejection fraction, or atrial fibrillation)
  • Patients must be 70 years or older
  • Patients must be technical and anatomical eligible for both interventions (as specified by Medtronic CoreValve(TM) for the TAVI procedure) after a formal consult by a cardiologist and a cardiovascular surgeon
  • Patients must be expected to survive more than one year after the intervention
  • Patients must be able to provide written informed consent as approved by the regional ethical committee after having received adequate information about the study
  • Patients must be able and agree to return to all post-procedural follow-up visits

Exclusion Criteria:

  • Isolated aortic valve insufficiency
  • Other significant heart valve disease requiring intervention
  • Coronary artery co-morbidity requiring revascularisation
  • Any previous open heart surgery
  • Myocardial infarction or percutaneous coronary intervention within the last year
  • Stroke or TIA within the last 30 days
  • Renal insufficiency requiring hemodialysis
  • Pulmonary insufficiency (FEV1 or diffusion capacity < 40% of expected)
  • Active infectious disease requiring antibiotics
  • Emergency intervention (within 24 hours after the indication for intervention has been made)
  • Unstable pre-interventional condition requiring inotropic support or mechanical heart assistance
  • A known hypersensitivity or contraindication to heparin or nitinol
  • Currently participating in an investigational drug or another device study
  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: NCT01057173

Locations
Denmark
Copenhagen University Hospital
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden, 413 45
Sponsors and Collaborators
Rigshospitalet, Denmark
Odense University Hospital
Sahlgrenska University Hospital, Sweden
Danish Heart Foundation
Copenhagen Trial Unit, Center for Clinical Intervention Research
Investigators
Principal Investigator: Daniel A Steinbrüchel, MD, DMSc Dep. of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University Hospital
Principal Investigator: Lars Søndergaard, MD, DMSc Dep. of Cardiology, Rigshospitalet, Copenhagen University Hospital
  More Information

Publications:
Responsible Party: Daniel Steinbruchel, MD, DMSc, professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01057173     History of Changes
Other Study ID Numbers: HA2009046
Study First Received: January 26, 2010
Last Updated: June 27, 2013
Health Authority: Denmark: National Board of Health

Keywords provided by Rigshospitalet, Denmark:
Heart Valve Disease
Heart Valve Prosthesis
Heart Valve Prosthesis Implantation
Randomized Controlled Trial

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

ClinicalTrials.gov processed this record on October 21, 2014