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Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis (AVATAR)

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ClinicalTrials.gov Identifier: NCT02436655
Recruitment Status : Recruiting
First Posted : May 7, 2015
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Marko Banovic, Clinical Centre of Serbia

Study Description
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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.

Condition or disease Intervention/treatment Phase
Aortic Stenosis Procedure: surgical aortic valve replacement Not Applicable

Detailed Description:

Aortic valve replacement (AVR) therapy is obvious choice in symptomatic severe aortic stenosis (AS) patients, because it improves symptoms, LV function and survival. Therefore, the accurate diagnosis of the disease, determination of its severity and precise evaluation of patients' clinical status is essential. However, the treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction (LV EF) are vague and the subject of ongoing debate. The most recent European and American guidelines have class I indication for AVR in asymptomatic severe AS patients with normal LV EF only in patients already scheduled for other cardiac surgery (for example by-pass surgery). In the case of symptom positive stress test American and European guideline differs, with European guidelines having class I indication and American guidelines only IIb indication. In all those cases of asymptomatic severe AS patients with normal LV EF the level of evidence is C, in other words there are no randomized trials. The consequence is that the decisions are made individually, patient by patient, and for this reason a patient with identical echocardiographic/clinical characteristics might be operated in USA but not in Europe (or any other part in the world), and vice-versa.

With the experience that has accumulated so far, there are retrospective and observational data that elective AVR might lead to favorable outcome compared to late (after symptom onset) surgery. This may especially come to attention with the understanding that annual risk of sudden cardiac death in asymptomatic severe AS patients with normal LV EF might be very similar or even a bit higher than operative mortality in experienced cardiac surgery centers.

Nevertheless, the majority of cardiologist worldwide are reluctant to send their asymptomatic patient with isolated severe AS and normal LV EF to AVR, and it will probably stay like that till randomized trials give us an answer whether elective AVR is beneficial.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 312 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial
Actual Study Start Date : June 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
No Intervention: conventional drug treatment
conservative treatment and watchful waiting till symptom onset (then aortic valve replacement). Other indications for aortic valve replacement include reduced left ventricular systolic function
Active Comparator: elective aortic valve replacement
elective aortic valve surgery (replacement) within 4 weeks after randomization
 Procedure: surgical aortic valve replacement
open heart aortic valve replacement


Outcome Measures
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Primary Outcome Measures :
  1. all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. in-hospital and 30 days operative mortality in operated patients in both groups [ Time Frame: 30 days ]
  2. repeat aortic valve surgery in operated patients in both groups [ Time Frame: 1 year ]
  3. major bleeding according to consensus report from the Bleeding Academic Research Consortium [ Time Frame: 1 year ]
  4. thromboembolic complications based on clinical symptoms, signs and imaging studies [ Time Frame: 1 year ]
  5. repeated major adverse cardiovascular events [ Time Frame: 1 year ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  • 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:

    1. Anginal chest pain during testing
    2. Syncope, dizziness during testing
    3. Decrease in systolic blood pressure during exercise ≥ 20mmHg
    4. 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
  • Impaired renal function, i.e. creatinine >200 µmol/L or glomerular filtration rate < 30 mL/min/1.73 m2
  • Significant pulmonary hypertension at rest (PASP > 50mmHg)
  • Uncontrolled hypertension at rest (systolic >180 mmHg and diastolic >100 mmHg)
  • Significant co-morbidity with reduced life expectance (< 3 years)
  • Uncontrolled Diabetes Mellitus (HbA1C > 9 %)
  • Significant COPD (FEV1 < 70% of predicted value)
  • Permanent or paroxysmal atrial fibrillation
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436655


Contacts
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Contact: Ivana M Živković, MD ivanazivkovic1985@gmail.com
Contact: Miodrag Jovanovic budimskivg@gmail.com

Locations
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Belgium
Cardiovascular Center Aalst Recruiting
Aalst, Belgium, 9320
Principal Investigator: Martin Penicka, MD, PhD         
Principal Investigator: Guy Van Camp, MD, PhD         
Croatia
University Clinical Center "Rebro" Recruiting
Zagreb, Croatia
Principal Investigator: Davor Milicic, MD, PhD         
Principal Investigator: Hrvoje Gasparovic, MD, PhD         
University Clinical Center ''Sestre milosrdnice'' Recruiting
Zagreb, Croatia
Contact: Nikola Pavlovic, MD    +385 1 3787 733    nikolap12@yahoo.com   
Principal Investigator: Šime Manola, MD,PhD         
Principal Investigator: Nikola Pavlovic, MD         
Czechia
University Hospital Brno Not yet recruiting
Brno, Czechia, 62500
Principal Investigator: Peter Nemec, MD,PhD         
Institute for Clinical and Experimental Medicine (IKEM) Recruiting
Prague, Czechia, 14021
Contact: Radka Kockova, MD, PhD         
Principal Investigator: Radka Kockova, MD,PhD         
Principal Investigator: Jiry Maly, MD, PhD         
France
Hôpital Cardiologique de Haut Lévèque Not yet recruiting
Pessac, France, 33604
Contact: Cecile Jore    + 33 5 57 65 64 37    cecile.jore@chu-bordeaux.fr   
Principal Investigator: Louis Labrousse, MD,PhD         
Ireland
Galway University Hospital Not yet recruiting
Galway, Ireland
Contact    +353 91 524222      
Principal Investigator: Faisal Sharif, MD         
Principal Investigator: Mark daCosta         
University Hospital Galway Recruiting
Galway, Ireland
Contact: Mark DaCosta         
Principal Investigator: Mark DaCosta, MD,PhD         
Lithuania
Vilnius University Hospital Santariskiu klinikos Recruiting
Vilnius, Lithuania, 08661
Contact       sigita.glaveckaite@santa.lt   
Principal Investigator: Sigita Glaveckaite, MD, PhD         
Poland
Medical University of Silesia Recruiting
Katowice, Poland, 40005
Principal Investigator: Wojciech Wojakowski, MD,PhD         
Principal Investigator: Marek Deja, MD, PhD         
Serbia
Cardiovascular Center 'Dedinje" Recruiting
Belgrade, Serbia, 11000
Contact: Srdjaen Boskovic, MD       boskovics@hotmail.com   
Principal Investigator: Srdjan Boskovic, MD         
Principal Investigator: Predrag Milojevic, MD         
CCSerbia Recruiting
Belgrade, Serbia, 11000
Contact: Marija Ristic    +381113663294    maraja18@gmail.com   
Contact: Gordana Isakovic    +381113613653      
University Clinical Centre Zvezdara Recruiting
Belgrade, Serbia, 11000
Contact: Natasa Cvetinovic, MD       ncvetinovic@gmail.com   
Principal Investigator: Goran Loncar, MD, PhD         
Insitute for Cardiovascular Diseases "Sremska Kamenica" Recruiting
Novi Sad, Serbia
Contact    0214805100    info@ikvbv.ns.ac.rs   
Principal Investigator: Ilija Srdanovic, MD,PhD         
Principal Investigator: Lazar Velicki, MD,PhD         
Spain
Hospital Universitario de Canarias Not yet recruiting
Tenerife, Spain
Contact: Dominguez-Rodriguez         
Principal Investigator: Alberto Dominguez-Rodriguez, MD, PhD         
Sponsors and Collaborators
Clinical Centre of Serbia
Investigators
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Principal Investigator: 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
More Information
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Publications:
Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schäfers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M; ESC Committee for Practice Guidelines (CPG); Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2012 Oct;42(4):S1-44. doi: 10.1093/ejcts/ezs455. Epub 2012 Aug 25.

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Responsible Party: Marko Banovic, MD PhD, FESC, FACC, Assistant Professor, Clinical Centre of Serbia
ClinicalTrials.gov Identifier: NCT02436655     History of Changes
Other Study ID Numbers: FWA00011929
First Posted: May 7, 2015    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019

Keywords provided by Marko Banovic, Clinical Centre of Serbia:
aortic stenosis
normal ejection fraction
asymptomatic

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