Severe Aortic Valve DiseaseCRYSTALNCT07368322
Comparative Research of Y-Incision vs. Standard Techniques for Aortic Root EnLargement
A study testing Y incision Technique (YIT) and Standard surgical enlargement techniques in people with Severe Aortic Valve Disease and Aortic Valve Replacement (AVR), run by willner nadav MD at 1 site in Israel.
Trial summary
Abstract Background: Aortic valve replacement (AVR) is crucial for patients with severe aortic valve disease. However, managing those with a small aortic annulus (SAA, i.e., annulus diameter < 22 mm) is challenging because implanting a small prosthesis can result in patient-prosthesis mismatch (PPM), suboptimal… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Severe Aortic Valve Disease, Aortic Valve Replacement (AVR), Small Aortic Annulus
- What is being tested?
- Y incision Technique (YIT) and Standard surgical enlargement techniques
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteIsrael
- Study dates
- 4 Jan 2026to Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18-80 years.
- Patients must have signed and dated an ICF in accordance with regulatory and institutional guidelines before any protocol-related procedures and must be willing and able to comply with scheduled visits.
- Diagnosed with aortic valve disease requiring aortic valve replacement.
- Patients with small aortic annulus relative to body size where conventional AVR result in moderate or severe PPM (defined as cases where the largest prosthesis that can be implanted in the native annulus would provide a predicted iEOA ≤0.85 cm²/m² for BMI <30, or ≤0.70 cm²/m² for BMI ≥30), based on manufacturer specifications and patient BSA).
- Suitable candidates for surgery as determined by the heart team.
Who cannot join
- Patients for whom conventional AVR without root enlargement is not expected to result in patient-prosthesis mismatch.
- Prior cardiac surgery.
- Severe concomitant valvular disease requiring additional procedures.
- Active endocarditis.
- Severe chronic lung disease
- Pre-existing lower limb deficits or any other medical comorbidities that interfere significantly with gait or the ability to perform exercise testing on a bicycle ergometer
Show all 9Show fewer
- Severe left ventricular dysfunction (LVEF < 30%).
- Contraindications to surgery.
- Concurrent active treatment in another clinical trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Rambam Health Care Campus
Haifa, 210961
Nadav Willner, MD, +972-50-8845456, n_willner@rmc.gov.il
About this study
Official title: Comparative Analysis of Standard Surgical Techniques vs. "Y Incision" Technique for Aortic Root Enlargement in Patients With Small Aortic Annulus Undergoing Aortic Valve Replacement: A Randomized Open-Label Controlled Trial (CRYSTAL Trial - Comparative Research of Y-Incision vs. Standard Techniques for Aortic Root EnLargement)
Abstract Background: Aortic valve replacement (AVR) is crucial for patients with severe aortic valve disease. However, managing those with a small aortic annulus (SAA, i.e., annulus diameter < 22 mm) is challenging because implanting a small prosthesis can result in patient-prosthesis mismatch (PPM), suboptimal hemodynamic outcomes, and reduced long-term survival. Traditional surgical techniques for aortic root enlargement (ARE), such as the Nicks and Manougian procedures, have significant limitations, typically allowing enlargement of only one to two prosthesis sizes and involving complex reconstructive procedures. The novel "Y incision" technique by Bo Yang offers a promising alternative, allowing implantation of valves up to five sizes larger than the native annulus, but it lacks comprehensive comparative data on its safety, efficacy, and functional outcomes.
Aim: This study aims to compare the safety outcomes, hemodynamic performance, and functional capacity of the "Y incision" technique versus standard surgical enlargement techniques in patients with a small aortic annulus undergoing AVR, with particular emphasis on objective functional assessment using cardiopulmonary exercise testing (CPET).
Read more
Methods: This prospective, randomized, controlled superiority trial will enroll patients with aortic valve disease and a small aortic annulus where conventional AVR is expected to result in moderate or severe PPM. Patients will be randomized 1:1 to either the standard surgical technique group or the "Y incision" technique group. Based on preliminary results and power calculations using the Win Ratio methodology, the sample size is set at 90 patients (45 in each group) to account for potential dropouts.
Primary Endpoint: Hierarchical composite endpoint analyzed using Win Ratio methodology, including (in order of priority): all-cause mortality, stroke, myocardial infarction, total hospitalization rate, moderate or severe PPM, exercise-induced valve dysfunction, and functional improvement at specified time points through 12 months.
Secondary Endpoints: Safety outcomes including intraoperative and 30-day complications, long-term anatomical complications, hemodynamic parameters assessed by echocardiography, functional outcomes measured by 6-minute walk distance and CPET (including peak VO₂), quality of life assessed using KCCQ questionnaire, and prosthetic valve-related outcomes at 3, 6, and 12 months post-surgery.
Conclusion: By providing robust, randomized controlled data with objective functional capacity assessment, this study aims to fill current gaps in knowledge regarding the long-term outcomes, safety profile, and functional benefits of the "Y incision" technique compared to standard surgical methods, potentially establishing evidence-based guidance for managing patients with a small aortic annulus undergoing AVR.
- Being tested
- Y incision Technique (YIT), Standard surgical enlargement techniques
- Keywords
- AVR, Aortic Root Enlargement, Small Aortic Annulus, Y Incision
- Medical subject headings
- Aortic Valve Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Y incision Technique (YIT)Procedure or surgery
A "Y"-shaped incision is made from the aortotomy, extending through the left coronary-noncoronary commissure into the aortomitral curtain. Thereafter, a Hemashield patch is sewn to the aortomitral curtain and the undermined aortic annulus, creating a larger space, and the bioprosthetic valve is placed and secured. Finally, the modified aortotomy is closed using the roof technique for better hemostasis and to enlarge the sinotubular junction and proximal ascending aorta. This technique allows the implantation of a valve up to five sizes larger than the native annulus.
Standard surgical enlargement techniquesProcedure or surgery
Traditional approaches include aortic root enlargement procedures such as the Nicks, Manougian, and Konno techniques; these procedures aim to widen the annulus and accommodate a larger prosthetic valve, thereby reducing the risk of PPM.
| Study group | Role | What they receive |
|---|---|---|
| Y-Incision Technique for Aortic Root Enlargement | Experimental | The novel "Y incision" technique by Bo Yang allows implantation of valves up to five sizes larger than the native annulus Receives: Procedure: Y incision Technique (YIT) |
| Standard Techniques for Aortic Root Enlargement | Active comparator | Traditional surgical techniques for aortic root enlargement (ARE), such as the Nicks and Manougian procedures, allow enlargement of only one to two prosthesis sizes and involve complex reconstructive procedures Receives: Procedure: Standard surgical enlargement techniques |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hierarchical composite of clinical and functional outcomes (Win Ratio)
A composite hierarchical endpoint analyzed using the Win Ratio methodology. Pairs of patients (one from each study arm) are compared based on a prioritized sequence of outcomes. The hierarchy is: 1. Time to all-cause mortality; 2. Incidence of stroke; 3. Incidence of myocardial infarction; 4. Frequency of total hospitalizations; 5. Presence of moderate/severe Prosthesis-Patient Mismatch (PPM); 6. Exercise-induced valve dysfunction; and 7. Improvement in functional status (defined as ≥1 NYHA class improvement). A "win" is assigned to the patient with the better outcome at each step.
Win Ratio - The ratio of the total number of wins in the intervention group to the total number of wins in the control group.
Measured: At specified time points through 12 months
Secondary outcomes (9)
Incidence of Major Adverse Events (MAE) through 12 months.
Number of participants experiencing intraoperative and 30-day complications, and long-term anatomical complications (including valve thrombosis or migration).
Unit of Measure: Number of participants.
Measured: Up to 12 months.
Change in Hemodynamic Parameters (Mean Pressure Gradient).
Assessment of the prosthetic valve mean pressure gradient as measured by transthoracic echocardiography.
Unit of Measure: mmHg.
Measured: Baseline, 3, 6, and 12 months.
Change in 6-Minute Walk Distance (6MWD).
Change from baseline in the distance walked during a 6-minute period. Unit of Measure: Meters.
Measured: Baseline and 12 months.
Change in Quality of Life (KCCQ-12 Score).
Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score. Scores range from 0 to 100, where higher scores represent better health status.
Unit of Measure: Points on a scale.
Measured: Baseline, 3, 6, and 12 months.
Change in Peak Oxygen Consumption (Peak VO2)
Peak VO2 attained during Cardiopulmonary Exercise Testing (CPET) using a standardized ramp protocol on a cycle ergometer or treadmill. Unit of Measure: mL/kg/min
Measured: Baseline and 12 months post-surgery.
Incidence of Prosthetic Valve-Related Complications
Number of participants experiencing specific valve-related adverse events, including prosthetic valve thrombosis, device migration, endocarditis, or structural valve deterioration (SVD) as defined by VARC-3 criteria.
Unit of Measure: Number of participants
Measured: 3, 6, and 12 months post-surgery.
Incidence of Early Postoperative Complications (30 Days)
A composite of safety events occurring within the early postoperative period, including major bleeding (BARC type 3 or 5), acute kidney injury (Stage 2 or 3), and new-onset permanent atrial fibrillation.
Unit of Measure: Number of participants
Measured: Within 30 days post-surgery.
Change in Effective Orifice Area (EOA)
The Effective Orifice Area of the prosthetic valve calculated via the continuity equation using transthoracic echocardiography (TTE) measurements. Unit of Measure: cm^2
Measured: Baseline, 3, 6, and 12 months post-surgery.
Change in NYHA Functional Classification
Assessment of heart failure symptoms according to the New York Heart Association (NYHA) Functional Classification. Scores range from Class I (no symptoms) to Class IV (severe symptoms).
Unit of Measure: NYHA Class (I, II, III, or IV)
Measured: Baseline, 3, 6, and 12 months post-surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start4 Jan 2026
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Aortic Valve DiseaseStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Y-Incision vs. Standard Techniques for Aortic Root Enlargement
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- willner nadav MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, willner nadav MD, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07368322
- Sponsor's protocol ID
- 0337-25-RMB
- Acronym
- CRYSTAL
- Status last verified
- Jan 2026
- First submitted
- 8 Jan 2026
- Last updated
- 26 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Analysis of Standard Surgical Techniques vs. "Y Incision" Technique for Aortic Root Enlargement in Patients With Small Aortic Annulus Undergoing Aortic Valve Replacement: A Randomized Open-Label Controlled Trial (CRYSTAL Trial - Comparative Research of Y-Incision vs. Standard Techniques for Aortic Root EnLargement)
- ClinicalTrials.gov ID
- NCT07368322
- Acronym / sponsor ID
- CRYSTAL / 0337-25-RMB
- Keywords
- AVR, Aortic Root Enlargement, Small Aortic Annulus, Y Incision
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- willner nadav MDUniversity, hospital or other
- Study start
- 4 Jan 2026 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 26 Jan 2026 (actual)
- 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.
Abstract Background: Aortic valve replacement (AVR) is crucial for patients with severe aortic valve disease. However, managing those with a small aortic annulus (SAA, i.e., annulus diameter < 22 mm) is challenging because implanting a small prosthesis can result in patient-prosthesis mismatch (PPM), suboptimal hemodynamic outcomes, and reduced long-term survival. Traditional surgical techniques for aortic root enlargement (ARE), such as the Nicks and Manougian procedures, have significant limitations, typically allowing enlargement of only one to two prosthesis sizes and involving complex reconstructive procedures. The novel "Y incision" technique by Bo Yang offers a promising alternative, allowing implantation of valves up to five sizes larger than the native annulus, but it lacks comprehensive comparative data on its safety, efficacy, and functional outcomes.
Aim: This study aims to compare the safety outcomes, hemodynamic performance, and functional capacity of the "Y incision" technique versus standard surgical enlargement techniques in patients with a small aortic annulus undergoing AVR, with particular emphasis on objective functional assessment using cardiopulmonary exercise testing (CPET).
Methods: This prospective, randomized, controlled superiority trial will enroll patients with aortic valve disease and a small aortic annulus where conventional AVR is expected to result in moderate or severe PPM. Patients will be randomized 1:1 to either the standard surgical technique group or the "Y incision" technique group. Based on preliminary results and power calculations using the Win Ratio methodology, the sample size is set at 90 patients (45 in each group) to account for potential dropouts.
Primary Endpoint: Hierarchical composite endpoint analyzed using Win Ratio methodology, including (in order of priority): all-cause mortality, stroke, myocardial infarction, total hospitalization rate, moderate or severe PPM, exercise-induced valve dysfunction, and functional improvement at specified time points through 12 months.
Secondary Endpoints: Safety outcomes including intraoperative and 30-day complications, long-term anatomical complications, hemodynamic parameters assessed by echocardiography, functional outcomes measured by 6-minute walk distance and CPET (including peak VO₂), quality of life assessed using KCCQ questionnaire, and prosthetic valve-related outcomes at 3, 6, and 12 months post-surgery.
Conclusion: By providing robust, randomized controlled data with objective functional capacity assessment, this study aims to fill current gaps in knowledge regarding the long-term outcomes, safety profile, and functional benefits of the "Y incision" technique compared to standard surgical methods, potentially establishing evidence-based guidance for managing patients with a small aortic annulus undergoing AVR.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Y-Incision vs. Standard Techniques for Aortic Root Enlargement
| Arm | Type | Receives |
|---|---|---|
| Y-Incision Technique for Aortic Root Enlargement | Experimental | Procedure: Y incision Technique (YIT)The novel "Y incision" technique by Bo Yang allows implantation of valves up to five sizes larger than the native annulus |
| Standard Techniques for Aortic Root Enlargement | Active comparator | Procedure: Standard surgical enlargement techniquesTraditional surgical techniques for aortic root enlargement (ARE), such as the Nicks and Manougian procedures, allow enlargement of only one to two prosthesis sizes and involve complex reconstructive procedures |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18-80 years.
- Patients must have signed and dated an ICF in accordance with regulatory and institutional guidelines before any protocol-related procedures and must be willing and able to comply with scheduled visits.
- Diagnosed with aortic valve disease requiring aortic valve replacement.
- Patients with small aortic annulus relative to body size where conventional AVR result in moderate or severe PPM (defined as cases where the largest prosthesis that can be implanted in the native annulus would provide a predicted iEOA ≤0.85 cm²/m² for BMI <30, or ≤0.70 cm²/m² for BMI ≥30), based on manufacturer specifications and patient BSA).
- Suitable candidates for surgery as determined by the heart team.
Key exclusion criteria (9 listed)
- Patients for whom conventional AVR without root enlargement is not expected to result in patient-prosthesis mismatch.
- Prior cardiac surgery.
- Severe concomitant valvular disease requiring additional procedures.
- Active endocarditis.
- Severe chronic lung disease
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 |
|---|---|---|
| Y incision Technique (YIT)A "Y"-shaped incision is made from the aortotomy, extending through the left coronary-noncoronary commissure into the aortomitral curtain. Thereafter, a Hemashield patch is sewn to the aortomitral curtain and the undermined aortic annulus, creating a larger space, and the bioprosthetic valve is placed and secured. Finally, the modified aortotomy is closed using the roof technique for better hemostasis and to enlarge the sinotubular junction and proximal ascending aorta. This technique allows the implantation of a valve up to five sizes larger than the native annulus. | Procedure or surgery | Y-Incision Technique for Aortic Root Enlargement |
| Standard surgical enlargement techniquesTraditional approaches include aortic root enlargement procedures such as the Nicks, Manougian, and Konno techniques; these procedures aim to widen the annulus and accommodate a larger prosthetic valve, thereby reducing the risk of PPM. | Procedure or surgery | Standard Techniques for Aortic Root Enlargement |
Primary outcome
Hierarchical composite of clinical and functional outcomes (Win Ratio)
Time frame: At specified time points through 12 months
A composite hierarchical endpoint analyzed using the Win Ratio methodology. Pairs of patients (one from each study arm) are compared based on a prioritized sequence of outcomes. The hierarchy is: 1. Time to all-cause mortality; 2. Incidence of stroke; 3. Incidence of myocardial infarction; 4. Frequency of total hospitalizations; 5. Presence of moderate/severe Prosthesis-Patient Mismatch (PPM); 6. Exercise-induced valve dysfunction; and 7. Improvement in functional status (defined as ≥1 NYHA class improvement). A "win" is assigned to the patient with the better outcome at each step. Win Ratio - The ratio of the total number of wins in the intervention group to the total number of wins in the control group.
9 secondary outcomes
Incidence of Major Adverse Events (MAE) through 12 months.
Time frame: Up to 12 months.
Change in Hemodynamic Parameters (Mean Pressure Gradient).
Time frame: Baseline, 3, 6, and 12 months.
Change in 6-Minute Walk Distance (6MWD).
Time frame: Baseline and 12 months.
Change in Quality of Life (KCCQ-12 Score).
Time frame: Baseline, 3, 6, and 12 months.
Change in Peak Oxygen Consumption (Peak VO2)
Time frame: Baseline and 12 months post-surgery.
Incidence of Prosthetic Valve-Related Complications
Time frame: 3, 6, and 12 months post-surgery.
Incidence of Early Postoperative Complications (30 Days)
Time frame: Within 30 days post-surgery.
Change in Effective Orifice Area (EOA)
Time frame: Baseline, 3, 6, and 12 months post-surgery.
Change in NYHA Functional Classification
Time frame: Baseline, 3, 6, and 12 months post-surgery.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2026.
- Individual participant dataSharing planned: Undecided. Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Y incision Technique (YIT) and Standard surgical enlargement techniques in people with Severe Aortic Valve Disease and Aortic Valve Replacement (AVR), run by willner nadav MD at 1 site in Israel.
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 9 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: looking for participants now, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadav Willner, MD (+972-50-8845456, n_willner@rmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical composite of clinical and functional outcomes (Win Ratio) (time frame: At specified time points through 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jan 2026.