Aortic StenosisAVATARNCT02436655
Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis
A study testing surgical aortic valve replacement in people with Aortic Stenosis, run by Clinical Centre of Serbia at 14 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- surgical aortic valve replacement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 14 sitesin 9 countries
- Study dates
- Jun 2015to May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 22Show fewer
- 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
- 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
Trial locations and contacts
14 sites in 9 countries.
14 sites in 9 countries
Serbia4 sites
Cardiovascular Center 'Dedinje"
Belgrade, 11000
CCSerbia
Belgrade, 11000
University Clinical Centre Zvezdara
Belgrade, 11000
Insitute for Cardiovascular Diseases "Sremska Kamenica"
Novi Sad
Croatia2 sites
University Clinical Center "Rebro"
Zagreb
University Clinical Center ''Sestre milosrdnice''
Zagreb
Czechia2 sites
University Hospital Brno
Brno, 62500
Institute for Clinical and Experimental Medicine (IKEM)
Prague, 14021
Lithuania1 site
Vilnius University Hospital Santariskiu klinikos
Vilnius, 08661
About this study
Official title: Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Aortic Stenosis
- Being tested
- surgical aortic valve replacement
- Keywords
- aortic stenosis, normal ejection fraction, asymptomatic
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surgical aortic valve replacementProcedure or surgery
open heart aortic valve replacement
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: surgical aortic valve replacement |
What is being measured
The primary outcome is the main question the study is designed to answer.
all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment
Measured: 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
Measured: 5 years
Secondary outcomes (6)
in-hospital and 30 days operative mortality in operated patients in both groups
Measured: 30 days
repeat aortic valve surgery in operated patients in both groups
Measured: 5 years
major bleeding according to consensus report from the Bleeding Academic Research Consortium
Measured: 5 years
thromboembolic complications based on clinical symptoms, signs and imaging studies
Measured: 5 years
repeated major adverse cardiovascular events
Measured: 5 years
all-cause death + heart failure hospitalization
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2015 (estimated)
- Study startJun 2015
- Primary completionMay 2021
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinical Centre of Serbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marko Banovic, Clinical Centre of Serbia
- Investigators
- Marko Banovic, MD, PhD, FESC, FACC, Principal investigator, Cardiology Department, University Clinical Centre of SerbiaSvetozar Putnik, MD, PhD, Principal investigator, Cardiac Surgery Department, University Clinical Centre of Serbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02436655
- Sponsor's protocol ID
- FWA00011929
- Acronym
- AVATAR
- Status last verified
- Dec 2021
- First submitted
- 30 Apr 2015
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 26995381Banovic 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.
PubMed 29224644Banovic 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.
PubMed 34779220Banovic 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.
PubMed 39217448Zelis 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.
PubMed 32774184
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02436655
- Acronym / sponsor ID
- AVATAR / FWA00011929
- Conditions
- Aortic Stenosis
- Keywords
- aortic stenosis, normal ejection fraction, asymptomatic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Clinical Centre of SerbiaUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- May 2021 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 7 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Procedure: surgical aortic valve replacementelective aortic valve surgery (replacement) within 4 weeks after randomization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (22 listed)
- 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:
- Left ventricular ejection fraction < 50% at rest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surgical aortic valve replacementopen heart aortic valve replacement | Procedure or surgery | elective aortic valve replacement |
Primary outcome
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
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
6 secondary outcomes
in-hospital and 30 days operative mortality in operated patients in both groups
Time frame: 30 days
repeat aortic valve surgery in operated patients in both groups
Time frame: 5 years
major bleeding according to consensus report from the Bleeding Academic Research Consortium
Time frame: 5 years
thromboembolic complications based on clinical symptoms, signs and imaging studies
Time frame: 5 years
repeated major adverse cardiovascular events
Time frame: 5 years
all-cause death + heart failure hospitalization
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Background: PubMed 26995381Banovic 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.
- Background: PubMed 29224644Banovic 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.
- Results publication: PubMed 34779220Banovic 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.
- Derived from this study: PubMed 39217448Banovic 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.
- Derived from this study: PubMed 32774184Zelis 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.
Related trials for Aortic Stenosis
Recruiting
Systematic Ambulatory ECG Monitoring Following TAVI
Aortic Stenosis, Conduction Disturbances
RecruitingObservational study
Multicenter Study for the Validation of Willem AI: Aortic StenoSis Early Diagnosis With AI-electrocardiogram Study
Aortic Stenosis
RecruitingObservational study
Heart Failure and Aortic Stenosis Transcriptome
Heart Failure, Aortic Stenosis
Recruiting
Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial
Hypertrophic Obstructive Cardiomyopathy \(HOCM\), Left Ventricular Outflow Tract Obstruction
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marko Banovic, MD, PhD, FESC, FACC principal investigator
Cardiology Department, University Clinical Centre of Serbia
Svetozar Putnik, MD, PhD principal investigator
Cardiac Surgery Department, University Clinical Centre of Serbia
14 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing surgical aortic valve replacement in people with Aortic Stenosis, run by Clinical Centre of Serbia at 14 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Serbia, Croatia, Czechia, Belgium, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02436655, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2022.