NCT02825134

Brief Summary

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.

Trial Health

82
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
376

participants targeted

Target at P75+ for not_applicable

Timeline
37mo left

Started Jun 2016

Longer than P75 for not_applicable

Geographic Reach
5 countries

9 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress76%
Jun 2016Jun 2029

First Submitted

Initial submission to the registry

June 29, 2016

Completed
1 day until next milestone

Study Start

First participant enrolled

June 30, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 7, 2016

Completed
7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2024

Completed
5.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2029

Expected
Last Updated

April 9, 2024

Status Verified

April 1, 2024

Enrollment Period

7.6 years

First QC Date

June 29, 2016

Last Update Submit

April 6, 2024

Conditions

Aortic Valve StenosisCardiovascular DiseasesHeart DiseasesHeart Valve DiseasesVentricular Outflow Obstruction

Keywords

heart valve diseasevalvular bioprosthesisaortic valve replacementRandomized clinical trial

Outcome Measures

Primary Outcomes (1)

  • Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure) within one year after the procedure.

    VARC-3 definitions

    at one year post-procedural.

Secondary Outcomes (26)

  • Procedure time

    Intraoperative

  • Duration of index hospitalization

    Number of days from admission to discharge (expected an averge of 7 days)

  • Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure)

    at 1 month and yearly thereafter up to 10 years post-procedure

  • Composite rate of all-cause mortality, disabling stroke and rehospitalization (related to the procedure, the valve or heart failure)

    at 1 and 12 months, and yearly thereafter up to 10 years post-procedure

  • Rehospitalization both composite and individual of related to the procedure, the valve or heart failure)

    at 1 and 12 months, and yearly thereafter up to 10 years post-procedure

  • +21 more secondary outcomes

Study Arms (2)

Transcatheter aortic valve replacement

EXPERIMENTAL

Transcatheter aortic valve replacement

Device: Transcatheter aortic valve replacement

Surgical aortic valve replacement

ACTIVE COMPARATOR

Surgical aortic valve replacement

Device: Surgical aortic valve replacement

Interventions

Transcatheter aortic valve replacementDEVICE

Retrograde transfemoral transcatheter aortic valve replacement with any CE mark approved aortic bioprosthesis with or without concomitant percutaneous coronary intervention.

Also known as: Transcatheter aortic valve implantation, TAVR, TAVI
Transcatheter aortic valve replacement
Surgical aortic valve replacementDEVICE

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.

Also known as: SAVR
Surgical aortic valve replacement

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Aarhus University hospital

Aarhus, 8000, Denmark

Location

Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Helsinki University Central Hospital

Helsinki, FI00029, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Landspital

Reykjavik, 101, Iceland

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (3)

  • Jorgensen TH, Savontaus M, Willemen Y, Bleie O, Tang M, Angeras O, Niemela M, Gudmundsdottir IJ, Khokhar A, Sartipy U, Dagnegard H, Laine M, Ruck A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Prendergast B, Sondergaard L, Horsted Thyregod HG, De Backer O; NOTION-2 Investigators. Three-Year Follow-Up of the NOTION-2 Trial: TAVR Versus SAVR to Treat Younger Low-Risk Patients With Tricuspid or Bicuspid Aortic Stenosis. Circulation. 2025 Nov 11;152(19):1326-1337. doi: 10.1161/CIRCULATIONAHA.125.076678. Epub 2025 Aug 30.

    PMID: 40884768DERIVED

  • Jorgensen TH, Thyregod HGH, Blankenberg S, Leon M, Sondergaard L, Prendergast B, De Backer O. The low-risk TAVR trials-A critical appraisal of the current landscape. Am Heart J. 2026 Jan;291:10-13. doi: 10.1016/j.ahj.2025.07.070. Epub 2025 Jul 29.

    PMID: 40744194DERIVED

  • Jorgensen TH, Thyregod HGH, Savontaus M, Willemen Y, Bleie O, Tang M, Niemela M, Angeras O, Gudmundsdottir IJ, Sartipy U, Dagnegaard H, Laine M, Ruck A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Sondergaard L, De Backer O; NOTION-2 investigators. Transcatheter aortic valve implantation in low-risk tricuspid or bicuspid aortic stenosis: the NOTION-2 trial. Eur Heart J. 2024 Oct 5;45(37):3804-3814. doi: 10.1093/eurheartj/ehae331.

    PMID: 38747246DERIVED

MeSH Terms

Conditions

Aortic Valve StenosisCardiovascular DiseasesHeart DiseasesHeart Valve DiseasesVentricular Outflow Obstruction

Interventions

Transcatheter Aortic Valve Replacement

Condition Hierarchy (Ancestors)

Aortic Valve Disease

Intervention Hierarchy (Ancestors)

Heart Valve Prosthesis ImplantationCardiac Surgical ProceduresCardiovascular Surgical ProceduresSurgical Procedures, OperativeProsthesis ImplantationThoracic Surgical Procedures

Study Officials

  • Ole De Backer, MD; PhD

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

  • Hans GH Thyregod, MD, PhD

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

June 29, 2016

First Posted

July 7, 2016

Study Start

June 30, 2016

Primary Completion

February 1, 2024

Study Completion (Estimated)

June 1, 2029

Last Updated

April 9, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations

DK(2)FI(3)IC(1)NO(1)SE(2)