- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02825134
Comparison of TAVR With SAVR in Younger Low Surgical Risk Patients With Severe Aortic Stenosis (NOTION-2)
Nordic Aortic Valve Intervention Trial 2 - A Randomized Multicenter Comparison of Transcatheter Versus Surgical Aortic Valve Replacement in Younger Low Surgical Risk Patients With Severe Aortic Stenosis
A randomized clinical trial investigating transcatheter (TAVR) versus surgical (SAVR) aortic valve replacement in patients 75 years of age or younger suffering from severe aortic valve stenosis.
Study hypothesis: The clinical outcome (death of any cause, stroke and rehospitalization (related to the procedure, valve or heart failure)) obtained within one year after TAVR is non-inferior to SAVR.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
BACKGROUND: Acquired aortic valve stenosis (AS) is the most common heart valve disease in the Western World with a prevalence of 2-7% at the age of >65 years. If untreated, it may lead to heart failure and death. Surgical aortic valve replacement (SAVR) until recent years has been the definitive treatment for patients with severe symptomatic AS. A less invasive transcatheter aortic valve replacement (TAVR) has been developed and has been a treatment of choice mostly for elderly high risk or inoperable patients. As TAVR technology is continuously evolving and improving, it may be anticipated that it will become a valuable alternative - and even the preferred choice of treatment - for younger, low-risk patients with severe aortic valve stenosis in the near future. However, to date, there is no clinical evidence that supports this hypothesis.
AIM: The purpose of the study is to compare TAVR and SAVR with regard to the intra- and post-procedural morbidity and mortality rate, hospitalization length, functional capacity, quality of life, and valvular prosthesis function in younger, low risk patients with severe bicuspid or tricuspid AS, scheduled for aortic valve replacement.
POPULATION: Younger low risk patients with severe aortic valve stenosis, which are scheduled for aortic valve replacement using a bioprosthesis. Subjects fulfilling the inclusion criteria, not having any exclusion criteria, and consenting to the trial will be randomized 1:1 to TAVR or SAVR with 186 patients in each group.
DESIGN: The study is a randomized clinical multicenter trial. Central randomization with variable block size and stratification by gender and coronary comorbidity will be used. An independent event committee blinded to treatment allocation will adjudicate safety endpoints.
INTERVENTIONS:
TAVR: Any CE-Mark approved transcatheter aortic bioprosthesis may be used in the study, and the choice is at the discretion of the local TAVR team. The transfemoral TAVR procedure may be performed under general anaesthesia, local anaesthesia/conscious sedation, or local anesthesia. Percutaneous coronary intervention (PCI) can be performed up to 30 days prior to TAVR or as a hybrid procedure.
SAVR: The surgical SAVR technique follows standard protocol of the local department of cardio-thoracic surgery. The operation is performed under general anesthesia, which follows standard protocol of the department of anesthesiology. A commercial available surgical aortic bioprosthesis at the surgeons discretion will be implanted. Concomitant coronary artery bypass graft (CABG) surgery may be performed.
END POINTS: The primary endpoint is the composite rate of death of any cause, stroke and rehospitalization (related to the procedure, valve or heart failure) within one year after the procedure. Secondary endpoints are listed below. Follow-up will be performed after 1 and 12 months and yearly thereafter for a minimum of 10 years.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lars Søndergaard, MD; DMSc
- Email: Lars.Soendergaard.01@regionh.dk
Study Locations
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Copenhagen, Denmark, 2100
- Rigshospitalet, Copenhagen University Hospital
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Århus, Denmark, 8000
- Aarhus University Hospital
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Helsinki, Finland, FI00029
- Helsinki University Central Hospital
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Oulu, Finland, 90220
- Oulu University Hospital
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Turku, Finland, 20520
- Turku University Hospital
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Reykjavík, Iceland, 101
- Landspital
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Bergen, Norway, 5021
- Haukeland University Hospital
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Göteborg, Sweden, 413 45
- Sahlgrenska University Hospital
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Stockholm, Sweden, 171 76
- Karolinska University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 75 years or younger.
- Severe calcific AS (Valve area <1cm2 (or <0.6 cm2/m2) AND one of the two following criteria: mean gradient >40mmHg or peak jet velocity >4.0m/s, OR in presence of low flow, low gradient with reduced or normal LVEF<50%, a dobutamine stress echo should verify true severe AS rather than pseudo-AS
- Symptomatic with angina pectoris, dyspnea or exercise-induced syncope or near syncope OR asymptomatic with abnormal exercise test showing symptoms on exercise clearly related to AS or systolic LV dysfunction (LVEF <50%) not due to another cause.
- Anticipated usage of biological aortic valve prosthesis.
- Low risk for conventional surgery (STS Score <4%).
- Suitable for both SAVR and transfemoral TAVR.
- Life expectancy >1 year after the intervention.
- Informed consent to participate in the study after adequate information about the study before randomization and intervention.
Exclusion Criteria:
- Coronary artery disease, not suitable for both percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).
- Coronary angiogram with a SYNTAX-score >22.
- LVEF <25% without contractile reserve during dobutamine stress echocardiography.
- Porcelain aorta, which prevents open-heart surgery.
- Bicuspid valve with aorta ascendens diameter ≥45mm
- Severe femoral, iliac or aortic atherosclerosis, calcification, coarctation, aneurysm or tortuosity, which prevents transfemoral TAVR.
- Need for open heart surgery other than SAVR with or without CABG.
- Myocardial infarction within last 30 days
- Stroke or TIA within the last 30 days. NOTION-2, 01. February 2017, version 5 9
- Current endocarditis, intracardiac tumor, thrombus or vegetation.
- Ongoing severe infection requiring intravenous antibiotics.
- Unstable pre-procedural condition requiring intravenous inotropes or mechanical assist device (IABP, Impella) on the day of intervention.
- Kidney disease requiring dialysis or severely impaired lung function (FEV1 and/or diffusion capacity <40% of predicted).
- Allergy to heparin, iodid contrast agent, warfarin, aspirin or clopidogrel.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Transcatheter aortic valve replacement
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Retrograde transfemoral transcatheter aortic valve replacement with any CE mark approved aortic bioprosthesis with or without concomitant percutaneous coronary intervention.
Other Names:
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Active Comparator: Surgical aortic valve replacement
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Conventional surgical aortic valve replacement with a bioprosthesis using normothermic cardiopulmonary bypass and cold blood cardioplegia cardiac arrest with or without concomitant coronary artery bypass graft surgery.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure) within one year after the procedure.
Time Frame: at one year post-procedural.
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VARC-3 definitions
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at one year post-procedural.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Procedure time
Time Frame: Intraoperative
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hours
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Intraoperative
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Duration of index hospitalization
Time Frame: Number of days from admission to discharge (expected an averge of 7 days)
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days
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Number of days from admission to discharge (expected an averge of 7 days)
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Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure)
Time Frame: at 1 month and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 month and yearly thereafter up to 10 years post-procedure
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Composite rate of all-cause mortality, disabling stroke and rehospitalization (related to the procedure, the valve or heart failure)
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Rehospitalization both composite and individual of related to the procedure, the valve or heart failure)
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Composite rate of all-cause mortality and disabling stroke
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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All-cause mortality
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Cardiovascular mortality
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Non-cardiovascular mortality
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Stroke
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Disabling Stroke
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Non-disabling stroke
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Transient Ischemic attack
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Myocardial Infarction
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Endocarditis
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Valve Thrombosis
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Need for aortic valve re-intervention
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Bleeding (life-threatening or major)
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Vascular complication (major)
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 defintions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Acute kidney injury (stage 2 or 3)
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 defintions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Echocardiographic aortic bioprosthesis performance (degree of paravalvular leakage, valve area, mean gradient, prosthesis patient mismatch)
Time Frame: at discharge, 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at discharge, 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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NYHA functional class
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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NYHA functional class
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Need for permanent pacemaker
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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New onset atrial fibrillation captured on ECG
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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VARC-3 definitions
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Left ventricle remodeling as assesed by echocardiography
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Left ventricle internal diameter in diastoli
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Quality of life change from baseline
Time Frame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Kansas City Cardiomyopathy Questionnaire, scale 0 (worse) to 100 (better)
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at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ole De Backer, MD; PhD, Rigshospitalet, Denmark
- Principal Investigator: Hans GH Thyregod, MD, PhD, Rigshospitalet, Denmark
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-15019580
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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