Clinical trial NCT02825134: Comparison of TAVR With SAVR in Younger Low Surgical Risk Patients With Severe Aortic Stenosis
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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases
Ventricular Outflow Obstruction
Keywords: heart valve disease
valvular bioprosthesis
aortic valve replacement
Randomized clinical trial
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Symetis SA
name: Boston Scientific Corporation
name: Abbott
name: Edwards Lifesciences
First posted: 2016-07-07
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
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.
timeFrame: at one year post-procedural.
Secondary outcomes:
measure: Procedure time
timeFrame: Intraoperative
measure: Duration of index hospitalization
timeFrame: Number of days from admission to discharge (expected an averge of 7 days)
measure: Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure)
timeFrame: at 1 month and yearly thereafter up to 10 years post-procedure
measure: Composite rate of all-cause mortality, disabling stroke and rehospitalization (related to the procedure, the valve or heart failure)
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Rehospitalization both composite and individual of related to the procedure, the valve or heart failure)
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Composite rate of all-cause mortality and disabling stroke
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: All-cause mortality
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Cardiovascular mortality
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Non-cardiovascular mortality
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Stroke
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Disabling Stroke
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Non-disabling stroke
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Transient Ischemic attack
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Myocardial Infarction
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Endocarditis
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Valve Thrombosis
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Need for aortic valve re-intervention
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Bleeding (life-threatening or major)
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Vascular complication (major)
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Acute kidney injury (stage 2 or 3)
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Echocardiographic aortic bioprosthesis performance (degree of paravalvular leakage, valve area, mean gradient, prosthesis patient mismatch)
timeFrame: at discharge, 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: NYHA functional class
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Need for permanent pacemaker
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: New onset atrial fibrillation captured on ECG
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Left ventricle remodeling as assesed by echocardiography
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
measure: Quality of life change from baseline
timeFrame: at 1 and 12 months, and yearly thereafter up to 10 years post-procedure
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Copenhagen University Hospital
city: Århus
country: Denmark
facility: Aarhus University hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Reykjavík
country: Iceland
facility: Landspital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Ole De Backer, MD; PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Hans GH Thyregod, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: