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Aortic Valve StenosisNOTION-2NCT02825134

Comparison of TAVR With SAVR in Younger Low Surgical Risk Patients With Severe Aortic Stenosis

A study testing Transcatheter aortic valve replacement and Surgical aortic valve replacement in people with Aortic Valve Stenosis and Cardiovascular Diseases, run by Ole De Backer at 9 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Transcatheter aortic valve replacement and Surgical aortic valve replacement
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
376 participants
Where
9 sitesin 5 countries
Study dates
30 Jun 2016to Jun 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

9 sites in 5 countries.

9 sites in 5 countries

Finland3 sites
  • Helsinki University Central Hospital

    Helsinki, FI00029

  • Oulu University Hospital

    Oulu, 90220

  • Turku University Hospital

    Turku, 20520

Other trials in Finland

Denmark2 sites
  • Aarhus University hospital

    Aarhus, 8000

  • Rigshospitalet, Copenhagen University Hospital

    Copenhagen, 2100

Other trials in Denmark

Sweden2 sites
  • Sahlgrenska University Hospital

    Gothenburg, 413 45

  • Karolinska University Hospital

    Stockholm, 171 76

Other trials in Sweden

Iceland1 site
  • Landspital

    Reykjavik, 101

Other trials in Iceland

Norway1 site
  • Haukeland University Hospital

    Bergen, 5021

Other trials in Norway

About this study

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

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.

Read the 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.

Being tested
Transcatheter aortic valve replacement, Surgical aortic valve replacement
Keywords
heart valve disease, valvular bioprosthesis, aortic valve replacement, Randomized clinical trial
Medical subject headings
Aortic Valve Stenosis, Cardiovascular Diseases, Heart Diseases, Heart Valve Diseases, Ventricular Outflow Obstruction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transcatheter aortic valve replacementDevice

    Also called Transcatheter aortic valve implantation, TAVR, TAVI

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

  • Surgical aortic valve replacementDevice

    Also called SAVR

    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.

Study groups in NCT02825134
Study groupRoleWhat they receive
Transcatheter aortic valve replacementExperimentalTranscatheter aortic valve replacement
Receives: Device: Transcatheter aortic valve replacement
Surgical aortic valve replacementActive comparatorSurgical aortic valve replacement
Receives: Device: Surgical aortic valve replacement

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: at one year post-procedural.

Secondary outcomes (26)
  1. Procedure time

    hours

    Measured: Intraoperative

  2. Duration of index hospitalization

    days

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

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

    VARC-3 definitions

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

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

    VARC-3 definitions

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

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

    VARC-3 definitions

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

  6. Composite rate of all-cause mortality and disabling stroke

    VARC-3 definitions

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

  7. All-cause mortality

    VARC-3 definitions

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

  8. Cardiovascular mortality

    VARC-3 definitions

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

  9. Non-cardiovascular mortality

    VARC-3 definitions

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

  10. Stroke

    VARC-3 definitions

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

  11. Disabling Stroke

    VARC-3 definitions

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

  12. Non-disabling stroke

    VARC-3 definitions

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

  13. Transient Ischemic attack

    VARC-3 definitions

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

  14. Myocardial Infarction

    VARC-3 definitions

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

  15. Endocarditis

    VARC-3 definitions

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

  16. Valve Thrombosis

    VARC-3 definitions

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

  17. Need for aortic valve re-intervention

    VARC-3 definitions

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

  18. Bleeding (life-threatening or major)

    VARC-3 definitions

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

  19. Vascular complication (major)

    VARC-3 defintions

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

  20. Acute kidney injury (stage 2 or 3)

    VARC-3 defintions

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

  21. Echocardiographic aortic bioprosthesis performance (degree of paravalvular leakage, valve area, mean gradient, prosthesis patient mismatch)

    VARC-3 definitions

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

  22. NYHA functional class

    NYHA functional class

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

  23. Need for permanent pacemaker

    VARC-3 definitions

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

  24. New onset atrial fibrillation captured on ECG

    VARC-3 definitions

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

  25. Left ventricle remodeling as assesed by echocardiography

    Left ventricle internal diameter in diastoli

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

  26. Quality of life change from baseline

    Kansas City Cardiomyopathy Questionnaire, scale 0 (worse) to 100 (better)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2016 (estimated)
  2. Study start30 Jun 2016
  3. Primary completionFeb 2024
  4. Study completionJun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
376 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02825134
Sponsor's protocol ID
H-15019580
Acronym
NOTION-2
Status last verified
Apr 2024
First submitted
29 Jun 2016
Last updated
9 Apr 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 40884768
  • 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.

    PubMed 40744194
  • 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.

    PubMed 38747246

Questions about this trial

What is this clinical trial studying?

A study testing Transcatheter aortic valve replacement and Surgical aortic valve replacement in people with Aortic Valve Stenosis and Cardiovascular Diseases, run by Ole De Backer at 9 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Finland, Denmark, Sweden, Iceland, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02825134, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2024.

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