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

• ClinicalTrials.gov Identifier: NCT02436655
• Recruitment Status: Completed
• First Posted: May 7, 2015
• Last Update Posted: January 12, 2022
• Sponsor: Clinical Centre of Serbia
• Information provided by (Responsible Party): Marko Banovic, Clinical Centre of Serbia

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 157 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
• Actual Primary Completion Date: May 2021
• Actual Study Completion Date: May 2021

Arms and Interventions

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

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 ]
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 [ Time Frame: 5 years ]

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: 5 years ]
3. major bleeding according to consensus report from the Bleeding Academic Research Consortium [ Time Frame: 5 years ]
4. thromboembolic complications based on clinical symptoms, signs and imaging studies [ Time Frame: 5 years ]
5. repeated major adverse cardiovascular events [ Time Frame: 5 years ]
6. all-cause death + heart failure hospitalization [ Time Frame: 5 years ]

Eligibility Criteria

• 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

Locations

Belgium

Cardiovascular Center Aalst

Aalst, Belgium, 9320

Croatia

University Clinical Center "Rebro"

Zagreb, Croatia

University Clinical Center ''Sestre milosrdnice''

Zagreb, Croatia

Czechia

University Hospital Brno

Brno, Czechia, 62500

Institute for Clinical and Experimental Medicine (IKEM)

Prague, Czechia, 14021

France

Hôpital Cardiologique de Haut Lévèque

Pessac, France, 33604

Ireland

University Hospital Galway

Galway, Ireland

Italy

Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Lithuania

Vilnius University Hospital Santariskiu klinikos

Vilnius, Lithuania, 08661

Poland

Medical University of Silesia

Katowice, Poland, 40005

Serbia

Cardiovascular Center 'Dedinje"

Belgrade, Serbia, 11000

CCSerbia

Belgrade, Serbia, 11000

University Clinical Centre Zvezdara

Belgrade, Serbia, 11000

Insitute for Cardiovascular Diseases "Sremska Kamenica"

Novi Sad, Serbia

Sponsors and Collaborators

Clinical Centre of Serbia

Investigators

• 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

  Study Documents (Full-Text)

Documents provided by Marko Banovic, Clinical Centre of Serbia:

Statistical Analysis Plan  [PDF] January 4, 2021

More Information

Publications of Results:

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. 2021 Nov 13. doi: 10.1161/CIRCULATIONAHA.121.057639. [Epub ahead of print]

Other Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Review.

• Responsible Party: Marko Banovic, MD PhD, FESC, FACC, Assistant Professor, Clinical Centre of Serbia
• ClinicalTrials.gov Identifier: NCT02436655
• Other Study ID Numbers: FWA00011929
• First Posted: May 7, 2015
• Last Update Posted: January 12, 2022
• Last Verified: December 2021

Keywords provided by Marko Banovic, Clinical Centre of Serbia:

aortic stenosis; normal ejection fraction; asymptomatic

Additional relevant MeSH terms:

Aortic Valve Stenosis; Constriction, Pathologic; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction