Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis

NCT ID: NCT02436655

Last Updated: 2022-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2021-05-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

elective aortic valve replacement

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

Group Type: ACTIVE_COMPARATOR

surgical aortic valve replacement

Intervention Type: PROCEDURE

open heart aortic valve replacement

Interventions

surgical aortic valve replacement

open heart aortic valve replacement

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Centre of Serbia

OTHER

Sponsor Role: lead

Responsible Party

Marko Banovic

MD PhD, FESC, FACC, Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marko Banovic, MD, PhD, FESC, FACC

Role: PRINCIPAL_INVESTIGATOR

Cardiology Department, University Clinical Centre of Serbia

Svetozar Putnik, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardiac Surgery Department, University Clinical Centre of Serbia

Locations

Cardiovascular Center Aalst

Aalst, , Belgium

University Clinical Center "Rebro"

Zagreb, , Croatia

University Clinical Center ''Sestre milosrdnice''

Zagreb, , Croatia

University Hospital Brno

Brno, , Czechia

Institute for Clinical and Experimental Medicine (IKEM)

Prague, , Czechia

Hôpital Cardiologique de Haut Lévèque

Pessac, , France

University Hospital Galway

Galway, , Ireland

Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Vilnius University Hospital Santariskiu klinikos

Vilnius, , Lithuania

Medical University of Silesia

Katowice, , Poland

Cardiovascular Center 'Dedinje"

Belgrade, , Serbia

CCSerbia

Belgrade, , Serbia

University Clinical Centre Zvezdara

Belgrade, , Serbia

Insitute for Cardiovascular Diseases "Sremska Kamenica"

Novi Sad, , Serbia

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 26995381 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29224644 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34779220 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39217448 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32774184 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FWA00011929

Identifier Type: -

Identifier Source: org_study_id