Comparison of Transcatheter Versus Surgical Aortic Valve Replacement in Younger Low Surgical Risk Patients With Severe Aortic Stenosis (NOTION-2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02825134|
Recruitment Status : Recruiting
First Posted : July 7, 2016
Last Update Posted : June 30, 2021
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 (composite endpoint of all-cause mortality, MI and stroke) obtained within 1 year after TAVR is non-inferior to SAVR.
|Condition or disease||Intervention/treatment||Phase|
|Aortic Valve Stenosis Cardiovascular Diseases Heart Diseases Heart Valve Diseases Ventricular Outflow Obstruction||Device: Transcatheter aortic valve replacement Device: Surgical aortic valve replacement||Not Applicable|
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 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 496 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. Interim analysis is planned after the first 20 events included in the primary end-point (all-cause mortality, stroke or myocardial infarction).
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 all-cause mortality death, myocardial infarction and stroke within one year after the procedure (VARC-2 defintions). Secondary endpoints are listed below. Follow-up will be performed after 30 days, 3 months, 1 year and yearly thereafter for a minimum of 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||372 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||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|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||June 2029|
Experimental: Transcatheter aortic valve replacement
Transcatheter aortic valve replacement
Device: Transcatheter aortic valve replacement
Retrograde transfemoral transcatheter aortic valve replacement with any CE mark approved aortic bioprosthesis with or without concomitant percutaneous coronary intervention.
Active Comparator: Surgical aortic valve replacement
Surgical aortic valve replacement
Device: Surgical aortic valve replacement
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 Name: SAVR
- 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. ]VARC-2 definitions
- Device success (Absence of procedural mortality, correct positioning of a single valve into the proper anatomical location AND intended performanace of the prosthetic heart valve) [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Procedure time [ Time Frame: Intraoperative ]
- Duration of index hospitalization [ Time Frame: Number of days from admission to discharge (expected an averge of 7 days) ]
- Composite rate of all-cause mortality, myocardial infarction and stroke [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure) at 30 days, 2 years and then yearly fot at least 10 years after the procedure (VARC-2 defintion). [ Time Frame: at 30 days, 2 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Cardiovascular mortality [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Stroke or TIA [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Bleeding (life-threatening, major or minor) [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Vascular complication (major or minor) [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 defintions
- Acute kidney injury (stage 1, 2 or 3) [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 defintions
- Echocardiographic aortic bioprosthesis performance (degree of paravalvular leakage, valve area, mean gradient) [ Time Frame: Before discharge from index hospitalization (expected an average of 7 days), at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- NYHA functional class [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]
- Need for permanent pacemaker [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- New onset atrial fibrillation captured on ECG [ Time Frame: Within discharge from index hospitalization (expected an average of 7 days), at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Time-related valve safety (echocardiographic structural valve deterioration, prosthetic valve endocarditis, prosthetic valve thrombosis, thrombo-embolic events OR VARC bleeding) [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]VARC-2 definitions
- Left ventricle remodeling as assesed by echocardiography [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]
- 1-year overall costs in both treatment arms. [ Time Frame: 1 year ]
- Duration of stay on ICU after index procedure. [ Time Frame: Number of days from procedure to discharge from ICU ]
- Incidence of early safety (all-cause mortality, all-stroke, life-threatening bleeding, acute kidney injury, coronary artery obstruction requiring intervention, Major vascular complication OR valve-related dysfunction requiring repeat procedure) [ Time Frame: at 30 days from index procedure ]VARC-II definitions
- Clinical efficacy (all-cause mortality, all stroke, requiring hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA class III or IV OR echocardiographic valve-related dysfunction) [ Time Frame: After 30 days of index procedure ]VARC-II definitions
- Quality of life change from baseline [ Time Frame: at 30 days, 1 year and annually thereafter up to 10 years post-procedure ]assesed by SF-36v2, EQ-5d and KCCQ
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02825134
|Contact: Lars Søndergaard, MD; DMSc||Lars.Soendergaard.firstname.lastname@example.org|
|Rigshospitalet, Copenhagen University Hospital||Recruiting|
|Copenhagen, Denmark, 2100|
|Contact: Lars Søndergaard Lars.Soendergaard.email@example.com|
|Contact: Peter S Olsen Peter.Skov.Olsen@regionh.dk|
|Aarhus University hospital||Recruiting|
|Århus, Denmark, 8000|
|Contact: Evald H Christiansen firstname.lastname@example.org|
|Contact: Kaj Erik Klaaborg email@example.com|
|Helsinki University Central Hospital||Recruiting|
|Helsinki, Finland, FI00029|
|Contact: Mika Laine firstname.lastname@example.org|
|Oulu University Hospital||Recruiting|
|Oulu, Finland, 90220|
|Contact: Timo Mäkikallio email@example.com|
|Contact: Vesa Anttila firstname.lastname@example.org|
|Turku University Hospital||Recruiting|
|Turku, Finland, 20520|
|Contact: Mikko Savotaus email@example.com|
|Contact: Markus Malmberg firstname.lastname@example.org|
|Reykjavík, Iceland, 101|
|Contact: Ingibjörg J Gudmundsdóttir email@example.com|
|Haukeland University Hospital||Recruiting|
|Bergen, Norway, 5021|
|Contact: Öjvind Bleie firstname.lastname@example.org|
|Contact: Rune Haaverstad email@example.com|
|Oslo University Hospital||Recruiting|
|Oslo, Norway, 2009|
|Contact: Lars Aaberge firstname.lastname@example.org|
|Contact: Kjell-Arne Rein email@example.com|
|Sahlgrenska University Hospital||Recruiting|
|Göteborg, Sweden, 413 45|
|Contact: Truls Råmunddal Truls.Ramunddal@wlab.gu.se|
|Karolinska University Hospital||Recruiting|
|Stockholm, Sweden, 171 76|
|Contact: Andreas Rück firstname.lastname@example.org|
|Contact: Göran Källner email@example.com|
|Principal Investigator:||Lars Søndergaard, MD; DMSc||Rigshospitalet, Denmark|
|Principal Investigator:||Peter S Olsen||Rigshospitalet, Denmark|