Early Surgery for Patients With Asymptomatic Aortic Stenosis (ESTIMATE)

Many cardiologists are convinced that early surgery in asymptomatic aortic stenosis (AS) saves lives. However there is currently no direct evidence for this and most recommendations from the ESC/ EACTS or ACC/ AHA in this field are supported by Level-B or C evidence. Therefore, the investigators designed a randomized controlled trial to demonstrate whether early surgery improves mortality and morbidity of patients with asymptomatic severe AS and low operative risk.

Study Overview

• Status: Unknown
• Conditions: Aortic Valve Stenosis; Aortic Valve Surgery
• Intervention / Treatment: Other: Early surgical aortic valve replacement; Other: Delayed Surgical aortic valve replacement

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Recruiting
    • Henri Mondor Hospital
    • Contact: Jean-Luc MONIN, MD PhD; Phone Number: +33 (0)1 49 81 28 10; Email: jean-luc.monin@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Adult patient, aged between 18 and 80 years (18 ≤ age ≤80)
• Low operative risk, defined as EuroSCORE II ≤ 5%
• No symptom potentially attributable to AS: no dyspnea, angina or syncope during exercise
• No class I indication for surgery
• No symptom/ fall in blood pressure during exercise test
• Severe AS according to current echocardiography criteria: Vmax > 4.0 m/s and/ or MPG > 40 mm Hg); AVA < 1.0 cm2 (not mandatory)
• Preserved LV systolic function: LVEF >50% according to echocardiography ; no LV wall motion abnormality
• Signed informed consent

Exclusion criteria

• Moderate/ high operative risk for aortic valve replacement, defined as EuroSCORE II > 5%
• Class-I indication for AVR (ESC-EACTS 2012, ACC/ AHA 2014) or fall in blood pressure during exercise testing (Class-IIa)
• Other indication for cardiac surgery (CABG, thoracic aorta)
• Positive exercise test including A/ unmasking of symptoms (angina, dyspnea at low workload, dizziness or syncope) during exercise or B/ Fall in systolic blood pressure during exercise below the baseline value.
• Patients unable to perform the exercise ECG
• More than mild AR (>grade 2/4)/ other significant valve disease LVEF ≤ 50%
• Serum creatinine >160 μmol/L
• Serious extra cardiac comorbidity/ life expectancy <2 years
• Patient included in another trial with signed informed consent
• Patient not affiliated to social insurance
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early surgery; Surgical aortic valve replacement	Other: Early surgical aortic valve replacement
Active Comparator: Delayed surgery according to guidelines; Surgical aortic valve replacement	Other: Delayed Surgical aortic valve replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combination of overall mortality and cardiac morbidity	Any adverse cardiac event requiring hospitalization. Adverse cardiac events include: 1/ development of any symptom clearly related to AS (dyspnea, angina, pre-syncope or syncope during exercise); 2/ major adverse cardiac events defined as congestive heart failure or acute coronary syndrome; 3/ death of any cause, including cardiac death.	1 year after randomization.

Secondary Outcome Measures

Outcome Measure	Time Frame
Each items of the composite criteria, overall and cardiovascular mortality and cardiac morbidity	1 year after randomization
Number of patients with preserved LV systolic function ( LVEF >50% according to echocardiography ) in each group	assessed at 3 months after surgery
Performance capacities assessed by speckle-tracking imaging (longitudinal function) in each group	assessed at 3 months after surgery
Postoperative Exercise test (Exercise Electrocardiogram)	assessed at 3 months after surgery

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jean-Luc MONIN, MD PhD., Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Monin JL, Lancellotti P, Monchi M, Lim P, Weiss E, Pierard L, Gueret P. Risk score for predicting outcome in patients with asymptomatic aortic stenosis. Circulation. 2009 Jul 7;120(1):69-75. doi: 10.1161/CIRCULATIONAHA.108.808857. Epub 2009 Jun 22.
• Farre N, Gomez M, Molina L, Cladellas M, Ble M, Roqueta C, Ascoeta MS, Comin-Colet J, Vila J, Bruguera J. Prognostic value of NT-proBNP and an adapted monin score in patients with asymptomatic aortic stenosis. Rev Esp Cardiol (Engl Ed). 2014 Jan;67(1):52-7. doi: 10.1016/j.rec.2013.06.020. Epub 2013 Oct 20.
• Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jun 10;63(22):e57-185. doi: 10.1016/j.jacc.2014.02.536. Epub 2014 Mar 3. No abstract available. Erratum In: J Am Coll Cardiol. 2014 Jun 10;63(22):2489. Dosage error in article text.
• Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012 Oct;33(19):2451-96. doi: 10.1093/eurheartj/ehs109. Epub 2012 Aug 24. No abstract available.
• Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999 Jul 15;341(3):142-7. doi: 10.1056/NEJM199907153410302.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: December 8, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2017
• Last Update Submitted That Met QC Criteria: July 3, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Surgery; Stenosis; Aortic valve
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: AOM 140460

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No