Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis (TOPAS Study)

This study is currently recruiting participants.
Verified April 2013 by Laval University
Sponsor:
Information provided by (Responsible Party):
Philippe Pibarot, Laval University
ClinicalTrials.gov Identifier:
NCT01835028
First received: April 16, 2013
Last updated: NA
Last verified: April 2013
History: No changes posted
  Purpose

Low-flow, low-gradient (LF-LG) aortic stenosis (AS) may occur with depressed (i.e. Classical LF; CLF) or preserved (i.e. Paradoxical LF; PLF) LV ejection fraction (LVEF) and both situations are amongst the most challenging encountered in patients with valvular heart disease. Although, CLF-LG AS is recognized has an important clinical entity, current ACC/AHA-ESC guidelines however do not provide precise recommendations for clinical management of these patients . PLF-LG AS is a new entity recently described by our group, which is characterized by more pronounced LV concentric remodeling with smaller LV cavity size and a restrictive physiology leading to impaired LV filling, altered myocardial function, and a low-flow state. Up to recently, this entity was often misdiagnosed, leading to underestimation of AS severity and inappropriate delays for aortic valve replacement surgery (SAVR). The two main challenges in patients with CLF- or PLF- LG AS are to distinguish between a true-severe (TS) versus a pseudo-severe (PS) stenosis and to accurately quantify the extent of myocardial impairment. Unfortunately, the traditional resting and stress echocardiographic parameters currently used to assess the severity of valvular and myocardial dysfunction in patients with LF-LG AS are far from being optimal, and as a consequence, quantification of disease severity and therapeutic management may not be appropriate in a substantial proportion of these patients.

THE GENERAL OBJECTIVES of the TOPAS study are to develop and validate new parameters and biomarkers to improve the assessment of stenosis severity and myocardial impairment, the risk-stratification, and the clinical decision making in patients with LF-LG AS and to assess the impact of the different therapeutic strategies on patient outcomes.


Condition Intervention
Aortic Valve Stenosis
Other: Doppler-echocardiography
Radiation: Computed tomography
Other: Magnetic resonance imaging
Biological: Blood sample
Other: Stress Echocardiography

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis (TOPAS Study Phase III)

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • all-cause mortality [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 30-day mortality (for patients treated by SAVR or TAVR) [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]
  • cardiovascular mortality [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]
  • new major cardiovascular events as defined by VARC: myocardial infarction, stroke, vascular complications, and re-hospitalization for heart failure composite end-point of cardiovascular mortality and hospitalization for heart failure [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]
  • composite end-point of cardiovascular mortality and hospitalization for heart failure [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • (1) Stenosis severity: We will use the weight and calcification of the valve explanted at the time of SAVR as a flow-independent marker of stenosis severity [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]
  • Hemodynamic (LV function) outcome: The outcome variables will be the changes during follow-up in resting and peak stress values of stroke volume, LVEF, longitudinal strain and plasma levels of BNP; LV flow reserve; LV contractile reserve [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]
  • Functional outcome: Another important objective of treatment is to improve the patient's functional status and quality of life. The outcome variables will be the changes in Duke Activity Score Index and the 6-min walk test distance during follow-up [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood sample (lithium-heparin, EDTA), Tissue (explanted aortic valves)


Estimated Enrollment: 320
Study Start Date: June 2002
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Classical Low Flow Low Gradient Aortic Stenosis

Patients have:

  1. Every year: medical history, physical examination, clinical outcomes
  2. At baseline and 1 year:Resting and stress echocardiography, blood biomarkers
  3. At baseline : Computed Tomography, MRI
Other: Doppler-echocardiography Radiation: Computed tomography Other: Magnetic resonance imaging Biological: Blood sample Other: Stress Echocardiography
Paradoxical Low Flow Aortis Stenosis

Patients have:

  1. Every year: medical history, physical examination, clinical outcomes
  2. At baseline and 1 year:Resting and stress echocardiography, blood biomarkers
  3. At baseline : Computed Tomography, MRI
Other: Doppler-echocardiography Radiation: Computed tomography Other: Magnetic resonance imaging Biological: Blood sample Other: Stress Echocardiography

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

patients with moderate to severe aortic stenosis and Low Fow Low Gradiwnt , with Low and preserved Ejection Fraction wil be selected at primary care clinic

Criteria

Inclusion Criteria:

  • LVEF≤ 40%
  • Indexed aortic valve area (AVA) ≤ 0.6 cm²/m²
  • Mean transvalvular gradient < 40 mmHg

Exclusion criteria:

  • Pregnant or lactating women
  • advanced renal failure
  • tumor with metastasis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01835028

Contacts
Contact: Philippe Pibarot, DVM, PHD 418-656-8711 ext 5938 Philippe.Pibarot@med.ulaval.ca
Contact: Abdellaziz Dahou, MD 418-656-8711 ext 3239 abdellaziz.dahou@criucpq.ulaval.ca

Locations
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States
Contact: Maurice Sarano       sarano.maurice@mayo.edu   
United States, Pennsylvania
Pittsburgh Medical Center Not yet recruiting
Pittsburgh, Pennsylvania, United States
Contact: Joao Cavalcante       cavalcantejl@upmc.edu   
Austria
Viena General Hospital Recruiting
Vienna, Austria
Contact: Gerald Mundigler       gerald.mundigler@meduniwien.ac.at   
Belgium
CHU Start Tilman Not yet recruiting
Liège, Belgium
Contact: Patrizio Lancellotti       plancellotti@chu.ulg.ac.be   
Canada, Ontario
Ottawa Heart Institute University Recruiting
Ottawa, Ontario, Canada
Contact: Ian Burwash       iburwash@ottawaheart.ca   
Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Québec Recruiting
Québec, Quebec, Canada, G1V4G5
Contact: Philippe Pibarot, DVM, PHD    418-656-8711 ext 5938    Philippe.Pibarot@med.ulaval.ca   
Contact: Abdellaziz Dahou, MD    418-656-8711 ext 3239    abdellaziz.dahou@criucpq.ulaval.ca   
Canada
St Paul's Hospital, Vancouver Recruiting
Vancouver, Canada
Contact: Jonathon Leipsic       JLeipsic@providencehealth.bc.ca   
France
Hôpital La Timone Not yet recruiting
Marseille, France
Contact: Gilbert Habib       gilbert.habib@free.fr   
Hôpital Bichat Not yet recruiting
Paris, France
Contact: David Messika-Zeitoun       david.messika-zeitoun@bch.aphp.fr   
CHU, Rennes Not yet recruiting
Rennes, France
Contact: Erwan Donal       Erwan.DONAL@chu-rennes.fr   
Germany
University Hospital Recruiting
Munster, Germany
Contact: Helmut Baumgartner       helmut.baumgartner@ukmuenster.de   
Sponsors and Collaborators
Laval University
  More Information

Publications:

Responsible Party: Philippe Pibarot, Doctor, Laval University
ClinicalTrials.gov Identifier: NCT01835028     History of Changes
Other Study ID Numbers: MOP-57745
Study First Received: April 16, 2013
Last Updated: April 16, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Laval University:
Aortic Stenosis
Low Flow
Low Gradient
Left Ventricle
Echocardiography, Doppler

Additional relevant MeSH terms:
Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on April 15, 2014