Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis

Aortic Stenosis Clinical Trial

— AVATAR  

Official title:

Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02436655
• Other study ID #: FWA00011929
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: May 2021

Study information

• Verified date: December 2021
• Source: Clinical Centre of Serbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 randomized trial.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Procedure:
• surgical aortic valve replacement
open heart aortic valve replacement

Locations

Country	Name	City	State
Belgium	Cardiovascular Center Aalst	Aalst
Croatia	University Clinical Center "Rebro"	Zagreb
Croatia	University Clinical Center ''Sestre milosrdnice''	Zagreb
Czechia	University Hospital Brno	Brno
Czechia	Institute for Clinical and Experimental Medicine (IKEM)	Prague
France	Hôpital Cardiologique de Haut Lévèque	Pessac
Ireland	University Hospital Galway	Galway
Italy	Città della Salute e della Scienza di Torino	Turin	Piedmont
Lithuania	Vilnius University Hospital Santariskiu klinikos	Vilnius
Poland	Medical University of Silesia	Katowice
Serbia	Cardiovascular Center 'Dedinje"	Belgrade
Serbia	CCSerbia	Belgrade
Serbia	University Clinical Centre Zvezdara	Belgrade
Serbia	Insitute for Cardiovascular Diseases "Sremska Kamenica"	Novi Sad

Sponsors (1)

Lead Sponsor	Collaborator
Clinical Centre of Serbia

Countries where clinical trial is conducted

Belgium,  Croatia,  Czechia,  France,  Ireland,  Italy,  Lithuania,  Poland,  Serbia, 

References & Publications (3)

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. — View Citation

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. — View Citation

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 Co — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	in-hospital and 30 days operative mortality in operated patients in both groups		30 days
Secondary	repeat aortic valve surgery in operated patients in both groups		5 years
Secondary	major bleeding according to consensus report from the Bleeding Academic Research Consortium		5 years
Secondary	thromboembolic complications based on clinical symptoms, signs and imaging studies		5 years
Secondary	repeated major adverse cardiovascular events		5 years
Secondary	all-cause death + heart failure hospitalization		5 years