Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis

NCT02436655 | Completed DMC

• 1 other identifier: FWA00011929
• Study Type: interventional
• Target: 157
• Locations: 9 countries
• Sites: 14

Brief Summary

Whether to intervene in asymptomatic patients with severe aortic stenosis and normal left ventricular ejection fraction remains controversial. The investigators therefore try to compare clinical outcomes of elective aortic valve replacement to conventional treatment and watchful waiting strategy in a prospective randomized trial.

Conditions

Aortic Stenosis

Keywords

aortic stenosis; normal ejection fraction; asymptomatic

Outcome Measures

Primary Outcomes (2)

• all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment

  36 months

• all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment

  5 years

Secondary Outcomes (6)

• in-hospital and 30 days operative mortality in operated patients in both groups

  30 days

• repeat aortic valve surgery in operated patients in both groups

  5 years

• major bleeding according to consensus report from the Bleeding Academic Research Consortium

  5 years

• thromboembolic complications based on clinical symptoms, signs and imaging studies

  5 years

• repeated major adverse cardiovascular events

  5 years

Study Arms (2)

conventional drug treatment

NO INTERVENTION

conservative treatment and watchful waiting till symptom onset (then aortic valve replacement). Other indications for aortic valve replacement include reduced left ventricular systolic function

elective aortic valve replacement

ACTIVE COMPARATOR

elective aortic valve surgery (replacement) within 4 weeks after randomization

Procedure: surgical aortic valve replacement

Interventions

surgical aortic valve replacement PROCEDURE

open heart aortic valve replacement

elective aortic valve replacement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men and women of any ethnic origin aged ≥18 years
• Written informed consent
• V max across the aortic valve \> 4m/s or Pmean ≥ 40mmHg and AVA ≤ 1cm2 or AVAi ≤ 0.6cm2/m2 at rest
• Without reported symptoms
• Society of Thoracic Surgeons (STS) score \< 8%

You may not qualify if:

• Participation in another clinical trial within 30 days prior randomization
• Pregnant or nursing women
• Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol
• Positive stress-test defined as:
• Anginal chest pain during testing
• Syncope, dizziness during testing
• Decrease in systolic blood pressure during exercise ≥ 20mmHg
• Malignant arrhythmia during exercise testing (VT or VF)
• Left ventricular ejection fraction \< 50% at rest
• Very severe AS (defined as Vmax \> 5.5 m/s at rest)
• Significant disease of other valves (Mitral stenosis with Pmean \> 5mg, or any significant regurgitation ≥ 3+
• Recent AMI (\< 1 year)
• Need for additional by-pass surgery or for aortic root replacement (i.e Bentall) or ascending aorta in asymptomatic patients undergoing AVR
• Previous by-pass surgery
• Previous any heart valve surgery

Sponsors & Collaborators

• Clinical Centre of Serbia: lead

Study Sites (14)

Cardiovascular Center Aalst

Aalst, 9320, Belgium

Location

University Clinical Center "Rebro"

Zagreb, Croatia

Location

University Clinical Center ''Sestre milosrdnice''

Zagreb, Croatia

Location

University Hospital Brno

Brno, 62500, Czechia

Location

Institute for Clinical and Experimental Medicine (IKEM)

Prague, 14021, Czechia

Location

Hôpital Cardiologique de Haut Lévèque

Pessac, 33604, France

Location

University Hospital Galway

Galway, Ireland

Location

Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Location

Vilnius University Hospital Santariskiu klinikos

Vilnius, 08661, Lithuania

Location

Medical University of Silesia

Katowice, 40005, Poland

Location

Cardiovascular Center 'Dedinje"

Belgrade, 11000, Serbia

Location

CCSerbia

Belgrade, 11000, Serbia

Location

University Clinical Centre Zvezdara

Belgrade, 11000, Serbia

Location

Insitute for Cardiovascular Diseases "Sremska Kamenica"

Novi Sad, Serbia

Location

Related Publications (5)

• Banovic M, Iung B, Bartunek J, Asanin M, Beleslin B, Biocina B, Casselman F, da Costa M, Deja M, Gasparovic H, Kala P, Labrousse L, Loncar Z, Marinkovic J, Nedeljkovic I, Nedeljkovic M, Nemec P, Nikolic SD, Pencina M, Penicka M, Ristic A, Sharif F, Van Camp G, Vanderheyden M, Wojakowski W, Putnik S. Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial. Am Heart J. 2016 Apr;174:147-53. doi: 10.1016/j.ahj.2016.02.001. Epub 2016 Feb 9.

  PMID: 26995381 BACKGROUND

• Banovic M, Iung B, Bartunek J, Penicka M, Vanderheyden M, Casselman F, van Camp G, Nikolic S, Putnik S. The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A protocol update. Am Heart J. 2018 Jan;195:153-154. doi: 10.1016/j.ahj.2017.10.005. Epub 2017 Oct 14. No abstract available.

  PMID: 29224644 BACKGROUND

• Banovic M, Putnik S, Penicka M, Doros G, Deja MA, Kockova R, Kotrc M, Glaveckaite S, Gasparovic H, Pavlovic N, Velicki L, Salizzoni S, Wojakowski W, Van Camp G, Nikolic SD, Iung B, Bartunek J; AVATAR Trial Investigators*. Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: The AVATAR Trial. Circulation. 2022 Mar;145(9):648-658. doi: 10.1161/CIRCULATIONAHA.121.057639. Epub 2021 Nov 13.

  PMID: 34779220 RESULT

• Banovic M, Putnik S, Da Costa BR, Penicka M, Deja MA, Kotrc M, Kockova R, Glaveckaite S, Gasparovic H, Pavlovic N, Velicki L, Salizzoni S, Wojakowski W, Van Camp G, Gradinac S, Laufer M, Tomovic S, Busic I, Bojanic M, Ristic A, Klasnja A, Matkovic M, Boskovic N, Zivic K, Jovanovic M, Nikolic SD, Iung B, Bartunek J. Aortic valve replacement vs. conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial. Eur Heart J. 2024 Nov 8;45(42):4526-4535. doi: 10.1093/eurheartj/ehae585.

  PMID: 39217448 DERIVED

• Zelis JM, Tonino PAL, Pijls NHJ, De Bruyne B, Kirkeeide RL, Gould KL, Johnson NP. Coronary Microcirculation in Aortic Stenosis: Pathophysiology, Invasive Assessment, and Future Directions. J Interv Cardiol. 2020 Jul 22;2020:4603169. doi: 10.1155/2020/4603169. eCollection 2020.

  PMID: 32774184 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Marko Banovic, MD, PhD, FESC, FACC

  Cardiology Department, University Clinical Centre of Serbia

  PRINCIPAL INVESTIGATOR

• Svetozar Putnik, MD, PhD

  Cardiac Surgery Department, University Clinical Centre of Serbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD, FESC, FACC, Assistant Professor

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: May 7, 2015
• Study Start: June 1, 2015
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: January 12, 2022

Record last verified: 2021-12

Locations

CZ (2); CR (2); IT (1); PL (1); FR (1); SE (4); IE (1); LI (1); BE (1)