Towards a More Standardized Bicuspid Aortic Valve Repair: Rationale and Design of CONTOUR Trial - a Randomized Trial

NCT06869954 | Recruiting

• 1 other identifier: 23-0625
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

Background: Between one-third and one-half of patients with bicuspid aortic valve (BAV) disease develop significant aortic regurgitation (AR) at a young age, leading to cardiomyopathy and heart failure. Aortic valve repair is an evolving and still underused strategy in BAV patients with AR. The lack of sufficient standardization remains the main limitation of current repair techniques, resulting in an increased risk of AR recurrence and reoperation. The most controversial issue is the stabilization of the BAV annulus. The CONTOUR trial aims to compare two different BAV annuloplasty concepts in a prospective randomized study. Methods: CONTOUR is a multicenter, randomized controlled trial designed to enroll 100 consecutive BAV patients with AR across four sites in Germany. BAV AR patients with an asymmetric configuration and without concomitant root aneurysm will be randomized 1:1 to undergo aortic valve repair using an internal HAART 200 annuloplasty device (i.e., INTERNAL group) (n=50) or external annuloplasty (i.e., double external ring annuloplasty) in the EXTERNAL group (n=50). 4D flow MRI will be performed preoperatively (t1), postoperatively at discharge (t2), and at 1-year follow-up (t3) for rater-blinded assessment of hemodynamic profiles (i.e., flow eccentricity) and regurgitation fraction at the MRI core-lab. Two hierarchically ordered primary endpoints will be considered: (1) postoperative reduction of flow eccentricity at hospital discharge and (2) regurgitation fraction (%) at 1-year follow-up. Discussion: The CONTOUR trial is designed to test the hypothesis that an internal annuloplasty device, creating a completely symmetric post-repair BAV geometry, achieves superior aortic valve repair outcomes compared to external annuloplasty. If our hypothesis is confirmed, our study will significantly influence aortic valve repair practice and contribute to the refinement of guideline recommendations in the management of BAV patients with AR.

Conditions

Bicuspid Aortic Valve (BAV); Aortic Regurgitation Disease

Keywords

aortic regurgitation; aortic valve repair; annuloplasty; bicuspid aortic valve

Outcome Measures

Primary Outcomes (2)

• Post-repair reduction of flow eccentricity in percent assessed via cardiac magnetic resonance imaging (MRI)

  Flow eccentricity (in percent) will be assessed using cardiac with phase-contrast imaging. Flow eccentricity is calculated based on the deviation of the flow jet from the center of the vessel lumen. Measurements will be performed pre- and post-repair to determine the percentage reduction in flow eccentricity. Measurements will be performed pre- and post-repair to determine the percentage reduction in flow eccentricity.

  Between the preoperative baseline (max. 30 days preoperative) (t1) and postoperative (pre-discharge) (t2) periods

• Regurgitation fraction in percent assessed via cardiac magnetic resonance imaging (CMR)

  The regurgitation fraction (%) will be assessed using cardiac magnetic resonance imaging (CMR) with phase-contrast imaging. Regurgitation fraction is calculated as the percentage of retrograde blood flow relative to the total blood flow through the valve. Measurements will be performed at baseline (pre-repair) and after the intervention (post-repair) to evaluate changes in regurgitation fraction. For the second primary endpoint (regurgitation fraction), the dependent variable is the post (t2 and t3) value. The study group, time post-surgery (t2 and t3), the interaction between the study group and time post-surgery measurement, and center are included as independent fixed-effect variables.

  Measurements will be taken at baseline (t1), an early post-operative time point (t2), and at 1-year follow-up (t3). The primary analysis will assess changes from baseline (t1) to both post-operative time points (t2 and t3).

Secondary Outcomes (10)

• Severity of aortic regurgitation (mild/moderate/severe)*

  Assessment at month 6 (t2) and month 12 (t3) in both study groups

• Transvalvular gradient (mmHg)

  Assessment at month 6 (t2) and month 12 (t3) in both study groups

• All-cause mortality (yes/no)

  Assessment at month 6 (t2) and month 12 (t3) in both study groups

• Adverse cardiac events (MACCE) (yes/no)

  Assessment at month 6 (t2) and month 12 (t3) in both study groups

• Aortic valve re-intervention (yes/no)

  Assessment at month 6 (t2) and month 12 (t3) in both study groups

Study Arms (2)

INTERNAL Group

ACTIVE COMPARATOR

For the INTERNAL group, the HAART 200 internal annuloplasty ring (CorCym, London, UK), specifically designed for BAV morphology, will be used for all patients. Intraoperative sizing for the internal ring is based on the geometric orientation and size of the non-fused cusp. A standard ball sizer is used for the measurement of the non-fused cusp to assess commissural orientation and surface area of the non-fused cusp. Sizing typically results in values of 23mm or 25mm, with other sizes being very rare. Both commissural posts of the internal annuloplasty ring are fixed using two subcommissural sutures \[10\]. A modified technique for placement of transannular looping sutures will be used to secure the internal ring in the subannular position, as recently published \[21\]. Cusp maneuvers (i.e., shaving, thinning of the raphe, central plication sutures) will be performed to achieve an effective height of 8-10 mm. When indicated (i.e., for ascending aortic diameter \> 45mm or aiming to achieve t

Device: Internal HAART 200 annuloplasty device

EXTERNAL group

ACTIVE COMPARATOR

For the EXTERNAL group, all study patients will undergo double external Dacron ring annuloplasty by simultaneous stabilization of the basal virtual ring and the STJ \[22\]. The surgical technique of double external annuloplasty, detailed by the Lansac group \[22\], involves aortic annulus sizing with a Hegar dilator to select the sizes of the external subannular annuloplasty ring and STJ ring (same size). After deep dissection of the aortic root, 6-7 2-0 pledgeted U sutures are placed circumferentially at the level of the virtual basal ring for external subannular ring implantation. Cusp maneuvers are performed similar to those in the INTERNAL group. STJ stabilization is achieved using an external STJ ring or ascending aortic replacement with a vascular tube graft (e.g., in cases with a high offspring of the right coronary artery). Treatment of the tubular ascending aorta is identical to the INTERNAL group.

Device: double external ring annuloplasty

Interventions

Internal HAART 200 annuloplasty device DEVICE

For the INTERNAL group, the HAART 200 internal annuloplasty ring (CorCym, London, UK), specifically designed for BAV morphology, will be used for all patients. Intraoperative sizing for the internal ring is based on the geometric orientation and size of the non-fused cusp. A standard ball sizer is used for the measurement of the non-fused cusp to assess commissural orientation and surface area of the non-fused cusp. Sizing typically results in values of 23mm or 25mm, with other sizes being very rare. Both commissural posts of the internal annuloplasty ring are fixed using two subcommissural sutures \[10\]. A modified technique for placement of transannular looping sutures will be used to secure the internal ring in the subannular position, as recently published \[21\]. Cusp maneuvers (i.e., shaving, thinning of the raphe, central plication sutures) will be performed to achieve an effective height of 8-10 mm. When indicated (i.e., for ascending aortic diameter \> 45mm or aiming to achieve th

INTERNAL Group

double external ring annuloplasty DEVICE

For the EXTERNAL group, all study patients will undergo double external Dacron ring annuloplasty by simultaneous stabilization of the basal virtual ring and the STJ \[22\]. The surgical technique of double external annuloplasty, detailed by the Lansac group \[22\], involves aortic annulus sizing with a Hegar dilator to select the sizes of the external subannular annuloplasty ring and STJ ring (same size). After deep dissection of the aortic root, 6-7 2-0 pledgeted U sutures are placed circumferentially at the level of the virtual basal ring for external subannular ring implantation. Cusp maneuvers are performed similar to those in the INTERNAL group. STJ stabilization is achieved using an external STJ ring or ascending aortic replacement with a vascular tube graft (e.g., in cases with a high offspring of the right coronary artery). Treatment of the tubular ascending aorta is identical to the INTERNAL group.

EXTERNAL group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of fused BAV phenotype with an asymmetric configuration (commissural orientation \< 170 degree) \[14\]
• Severe aortic regurgitation (vena contracta (vc) \> 6mm and/or pressure half-time (PHT) \< 200 ms and/or effective regurgitant orifice area (EROA) \> 30 mm2 and/or regurgitant volume (RV) \> 60 ml/beat and/or left ventricular end-systolic diameter (LVESD) \> 50mm (or indexed LVESD \> 20mm/m2 BSA) and/or regurgitation fraction (RF) in cardiothoracic MRI \> 40%) (at least one parameter is required) \[15\]
• Isolated aortic valve surgery or concomitant procedure (including CABG and/or mitral/tricuspid valve surgery and/or ascending aortic surgery)
• Willingness to participate and written informed consent
• Age at surgery \> 18 years

You may not qualify if:

• Moderate/severe BAV stenosis (pmean \> 20mmHg)
• Moderate/severe BAV cusp calcifications extending beyond the raphe region and/or necessitating patch implantation (deemed irreparable based on preoperative TOE (as by decision of the operating surgeon)
• Concomitant aortic root aneurysm \> 45mm requiring simultaneous aortic root surgery \[16\]
• Acute/subacute BAV endocarditis
• Contraindication to MRI

Sponsors & Collaborators

• University Hospital Augsburg: lead
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• University Clinic Frankfurt: collaborator
• Heart Center Leipzig - University Hospital: collaborator

Study Sites (4)

University Hospital Augsburg

Augsburg, Bavaria, 86156, Germany

RECRUITING

University Heart and Vascular Center Frankfurt

Frankfurt am Main, Hesse, 60598, Germany

NOT YET RECRUITING

Heart Center Leipzig

Leipzig, Saxony, 04289, Germany

NOT YET RECRUITING

Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Related Publications (1)

• Girdauskas E, Stock S, Hofbauer D, Petersen J, Reichenspurner H, Holubec T, Walther T, Vogl T, Borger M, Gutberlet M, Kroncke T, Decker J, Zapf A, Lezius S, Lenz A, Lansac E, Bannas P. Towards a More Standardized Bicuspid Aortic Valve Repair: Rationale and Design of the CONTOUR Trial. Eur J Cardiothorac Surg. 2025 Dec 1;67(12):ezaf360. doi: 10.1093/ejcts/ezaf360.

  PMID: 41124604 DERIVED

MeSH Terms

Conditions

Bicuspid Aortic Valve Disease; Aortic Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Aortic Valve Disease; Heart Valve Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Evaldas Girdauskas, Prof.

CONTACT

+49 821 4002671; evaldas.girdauskas@uk-augsburg.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Because of the multicentre design, a MRI Core Center has been established to ensure standardized and rater-blinded analysis of the collected 4D flow MRI endpoints. To avoid any potential human bias, study-related radiologists (P.B., A.L.) at the MRI Core Center who are not involved in the treatment of study patients and are blinded to the group assignment will assess MRI-data in the specific MRI database separated from the main project eCRF.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: CONTOUR is a prospective, randomized, parallel, two-arm, and assessor-blinded multicenter trial.

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: March 11, 2025
• Study Start: May 21, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)