Aortic Valve InsufficiencyNCT04162444
Results of the Aortic Valve Reconstruction in Children
An observational study of Aortic Valve Insufficiency, run by National Medical Research Center for Children's Health, Russian Federation at 1 site in Russia.
Trial summary
Aortic valve disease counts up to 5% of cases of congenital heart disease being one of the most common congenital malformations of the cardiovascular system. This disease requires replacement of the damaged valve which in itself is not a trivial task to complete in children as there is still no available best practice… Read more about this study
- Who is it for?
- Ages 29 days to 12 years
- Conditions the study is for
- Aortic Valve Insufficiency
- What is being tested?
- Physical examination, The Ross Classification for Heart Failure in Children and The Aristotle score
- How many people
- 40 participants
- Where
- 1 siteRussia
- Study dates
- 18 Feb 2020to Oct 2027
- Phase
- Observational
- 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 29 days to 12 years
- All sexes
- No healthy volunteers
- Child
Study population: The study will enroll the participants from the patients of the the Department of Cardiac Surgery with dysfunction of the native aortic valve with and without manifestations, with indications for the aortic valve reconstruction, and without concomitant supravalvular and subvalvular aortic stenosis and major congenital heart diseases.
Who may be able to join
- Age from 29 days to 12 years
- Patient's official caregivers have to sign the informed consent after they are thoroughly explained the meaning of the study, its protocol and timelines.
- Patients with manifestations, with mean gradient at the aortic valve >40 mmHg with normal left ventricular ejection fraction (LVEF), or patients with manifestations with the mean gradient < 40 mmHg with decreased LVEF, or patients with manifestations with severe aortic insufficiency, or patients without manifestations, but with decreased LVEF with aortic insufficiency, or patients with concomitant moderate aortic insufficiency and moderate aortic stenosis with manifestations.
- Aortic Z-score over -1,5
- Absence of subvalvular and supravalvular aortic stenosis
- Absence of intracardiac malformations requiring correction, except for septal defects
Show all 16Show fewer
- Non-inclusion criteria:
- Known hypersensitivity to aspirin, heparin, nitinol, intravenous contrast or contradictions to their administration due to other causes.
- Previous replacement of the aortic valve with mechanical or xenografts.
- Confirmed active sepsis or endocarditis.
- Hypoplasia of the fibrous ring of the aortic valve with Z score under -1,5.
- Life expectancy less than 3 years due to concomitant diseases.
- Participation in another clinical research.
- Indications for urgent surgery.
- Intracardiac malformations requiring momentary surgical correction.
- Geographical instability of a patient and his/her official caregivers, complicating significantly the constant contact during the study
Who cannot join
- Refusal of patient's caregivers to participate further in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
National Medical Research Center of Children's Health
Moscow, 119296
Aleksandr Lezhnev, PhD, MD, +79095391010, lezhnev.md@gmail.com
Anastacia Boliguzova, +79851522773, anboliguzova@gmail.com
About this study
Official title: Short-term and Midterm Results of the Aortic Valve Reconstruction With Autopericardium in Children
Aortic valve disease counts up to 5% of cases of congenital heart disease being one of the most common congenital malformations of the cardiovascular system. This disease requires replacement of the damaged valve which in itself is not a trivial task to complete in children as there is still no available best practice for valve replacement. Today, the following alternative variants are performed in children: mechanical aortic prosthesis, xenografts, allografts, and pulmonary autograft (Ross procedure) and each has its potential advantages and disadvantages.
Mechanical aortic prostheses require lifelong anticoagulation therapy and repeated surgeries to replace mechanical valves during child growth. Available xenografts in children also has suboptimal results not only because of absence of growth potential, but also due to development of degenerative changes in biological tissue of the graft leaflets. Allograft tissues are exposed to rapid biodegradation in the recipient body and thus requiring repeated surgeries associated with higher difficulty, high risk of hemorrhages, and injury of the coronary injuries. Ross procedure was proposed as theoretically the most evidence-based reconstruction of the aortic valve in children. Even successfully performed Ross operation transforms one-valve disorder into two-valve disease.
Read more
The accumulation of knowledge on the anatomy of the aortic root and improvement of surgical techniques led to the development of new methods for reconstruction of the valve function. The technique is widely applied in adult cardiac surgery, uses glutaraldehyde-treated autopericardium for augmentation of the leaflets. Absence of foreign material provides no need for anticoagulation therapy. Potentially, reconstruction of the aortic valve with autopericardium can be widely used in children.
Aim is to study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. Patients aged 29 days to 12 years will be included into the study. The data according to the protocol of the study will be assessed at the stage of inclusion, during the surgery, in 30 days after the surgery, and in 1, 2, and 3 years after the surgery. Data about all the patients included into the research will be analyzed in order to study the endpoints and achieve the research aim.
Read the detailed description
Aortic valve disease amounts to approximately 5% of the total number of cases of congenital heart disease, thus being one of the most common congenital malformations of the cardiovascular system. This disease requires replacement of the damaged valve, which in itself is not a trivial task to complete in children as there is still no available perfect option for valve replacement. Today, the following alternative variants for the aortic valve reconstruction in children are known: mechanical aortic prosthesis, xenografts, allografts and pulmonary autograft (Ross procedure); each of the above-mentioned variants has its potential advantages and disadvantages.
Mechanical aortic prostheses are widely available, including in small sizes (16 and 18 mm) appropriate for young children. However, the available sizes still do not allow to perform the surgical reconstruction in children of the first year of life. Besides these patients need lifelong anticoagulation therapy and necessity for repeated surgeries in order to replace mechanical valves with a child's growth.
Available xenografts have various types but usually, their sizes begin from 19 mm which does not fit for the majority of young children. Aortic xenografts are characterized by low risk of thromboembolism complications and do not require lifelong antithrombotic therapy. However, application of these grafts in children also has suboptimal results not only because of the absence of growth potential but also due to the development of degenerative changes in biological tissue of the graft leaflets.
Allografts are characterized by perfect hemodynamic parameters which are similar to the native healthy aortic valve. Risk of thromboembolic complications in implantation of allografts is very low, so there is no need for anticoagulation therapy. As in xenografts, allograft tissues are exposed to rapid biodegradation in the recipient body with the following development of obstruction or insufficiency and thus requiring a repeat operation. Implantation of allografts is associated with higher difficulty and high risk of hemorrhages and injury of the coronary injuries.
Ross procedure was proposed as theoretically the most justified choice for reconstruction of the aortic valve in children. As a conduit for reconstruction of the aortic valve the host's intact native pulmonary valve - autograft - is used; and the pulmonary valve is usually replaced by xenograft. Even successfully performed Ross operation, according to some authors, resolves the problem of the aortic valve only for a while; moreover, it causes another problem with the pulmonary valve, thus transforming one-valve disorder into two-valve disease.
The accumulation of knowledge on the anatomy of the aortic root and improvement of surgical techniques has led to the development of new methods for reconstruction of the valve function. The experience of various options for interventions on the aortic valve leaflet gained in adult cardiac surgery allowed to consider such interventions as an alternative method to valve reconstruction in children. About ten years ago, Professor Shigeyuki Ozaki brought the reconstruction of the aortic valve with the patient's own tissues to a completely new technological level. This technique includes the use of glutaraldehyde-treated autopericardium for augmentation of the leaflets; the reproducibility of the method was significantly increased due to usage of the template sets and special tools for the measurement of the native valve. Since no foreign material is used, there is no need for anticoagulation therapy after such intervention, which the authors of the method referred to as the valve reconstruction, not implantation of the graft. Potentially, reconstruction of the aortic valve with autopericardium can be widely used in children. In this population of patients, the various variants of the leaflets dysmorphogenesis are much more common, a wide range of morphological diversity of structure with inadequate hemodynamics can be found: monocuspid, bicuspid and pseudobicuspid valves; which does not allow to perform the valve reconstruction by restoring the original anatomy.
The normal anatomy of the aortic valve assumes three-valve structure, and most augmentation techniques suppose formation of tricuspid anatomy. At the same time, there is an alternative variant of hemodynamically adequate valve structure in the human body - bicuspid anatomy of the venous valves in the vena cava inferior system. Theoretical calculations obtained through computer simulation show that the neo-valve formed by three artificial leaflets will retain its locking function with increasing the diameter of the fibrous ring only by 8%. At the same time, the bicuspid valve with an increased height of the leaflets is able to maintain the shut-off function with an increase in the diameter of the fibrous ring by 67%.
The aim is to study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. Primary endpoints: patient's death due to various causes during the first 30 days after the surgery. Secondary endpoints for efficacy assessment: аreedom from repeated surgeries on the aortic valve; mean gradient at the aortic valve over 40 mmHg; аortic insufficiency over 2 degree; effective area of the neo-aortic valve less than 1.0 cm2/m2 Secondary endpoint for safety assessment: acute disorders of cerebral circulation within the first 30 days after the surgery; hemorrhage needing revision surgery; acute kidney injury, stages 2 or 3, including the necessity for renal replacement therapy; acute coronary syndrome; dysfunction of the neo-valve requiring repeated surgery.
Patients aged from 29 days to 12 years old with dysfunction of the native aortic valve with and without manifestations, with indications for the aortic valve reconstruction, and without concomitant supravalvular and subvalvular aortic stenosis and major congenital heart diseases, will be included into the study. The study design is planned to be prospective, cohort, single-center, observational. In total 40 patients will be included into the study. The data according to the protocol of the study will be assessed at the stage of inclusion, during the surgery, in 30 days after the surgery, and in 1, 2, and 3 years after the surgery. Data about all the patients included in the research will be analyzed in order to study the endpoints and achieve the research aim.
The first report on safety of the operation will be published when all the patients included in the study are carried out the procedure of augmentation of the aortic valve with autopericardium and all of them are examined within 30 days after the surgery. A report about the efficacy of the operation within the first year after the performed surgery of augmentation of the aortic valve with autopericardium; it will be published after all the patients included in the study are examined at the control visit in one year after the surgery. Report about clinical and hemodynamic efficacy of the operation within three years after the performed reconstruction of the aortic valve with autopericarduim; it will be published after all the patients included in the study are examined in three years after the surgery. Final report on the study will be published when for all patients included in the study all the follow-up periods are completed, or patients are excluded from the study due to other causes.
For compensation for the lost quantitative or qualitative data, statistical methods will not be applied. If there is a lack in patient's data due to any causes, such a patient will be excluded from this block of analysis. A number of patients included in each analysis will be represented in the report, so readers could themselves assess the influence of the lost data on the published result.
- Conditions
- Aortic Valve Insufficiency
- Being tested
- Physical examination, The Ross Classification for Heart Failure in Children, The Aristotle score, Assessment of administered specific therapy, Multispiral computed tomography/3D echocardiography
- Keywords
- Aortic Valve Insufficiency/surgery, Aortic Valve/surgery, Child, Reconstructive Surgical Procedures/methods, Cardiac Surgical Procedures, Hemodynamics, Pericardium/transplantation, Transplantation, Autologous, Treatment Outcome, Heart Valve Prosthesis Implantation
- Medical subject headings
- Aortic Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physical examinationDiagnostic test
Also called Medical examination, Clinical examination
A physical examination is a routine screening procedure used to investigate a patient's symptoms or complaints. It consists of a series of questions regarding patient medical history followed by an examination of the symptoms to determine the correct diagnosis and treatment plan.
The Ross Classification for Heart Failure in ChildrenDiagnostic test
Also called Assessment of heart failure according to Ross scale
The assessment is performed by pediatric cardiologist according to the classic Ross scale. One of the 4 classes of chronic heart failure is registered.
The Aristotle scoreDiagnostic test
Also called Assessment of surgical risks according to the ARISTOTLE score
Surgical risks will be assessed by the ARISTOTLE score developed specially for the task. The calculation will be performed online, available from http://www.aristotleinstitute.org.
Assessment of administered specific therapyOther
The data will be registered as groups of administered medicines:
- Antiplatelet agents
- Loop diuretics
- Potassium-sparing diuretics
- Angiotensin-converting enzyme inhibitors
Multispiral computed tomography/3D echocardiographyDiagnostic test
Also called MS-CT/3D-echo
All patients enrolled in the study should be routinely examined with multispiral computed tomography (MS-CT) or 3D-echo before surgery and 3 years later. As a result, a 3D aortic root reconstruction will be made to assess its size and anatomy and subsequently build a 3D soft model for surgery imitation.
At the study onset, we plan to perform MS-CT, then 3D-echo. If the correlation resulting from 3D-echo and the actual sizes will be high, the isolated 3D-echo will be preferred in the future.
If none of the methods is available, the patients will not be enrolled in the study.
The following data will be registered for further analysis:
- Perimeter of the aortic valve
- Diameter of the aortic valve at sinuses level
- Height of the aortic sinuses
- Morphology of the aortic valve
Transthoracic and transesophageal echocardiographyDiagnostic test
Transthoracic echocardiography is carried out at baseline, at discharge and then annually. It is performed in order to assess the contractile function of the heart and hemodynamic characteristics of the aortic valve and its autopericardium graft.
Transesophageal echocardiography is carried out directly after the withdrawal of the artificial circulation when performing augmentation of the aortic valve with autopericardium in order to asses hemodynamic characteristics of the aortic neo-valve.
12-lead electrocardiogramDiagnostic test
Also called 12-lead ECG
Registering 12-lead electrocardiogram (ECG) is used as a tool for assessment of the regularity of the heart rhythm as well as screening and predictive tool for assessment of fibrosis and hypertrophy processes in the myocardium. The following data will be registered:
- Heart rate
- Sinus rhythm (yes/no)
- Positive R wave in leads V5-6
- Angle α less than 0
- Presence/absence of abnormal Q wave
- Presence/absence of ST-segment depression in precordial leads
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | We will study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. Receives: Diagnostic Test: Physical examination; Diagnostic Test: The Ross Classification for Heart Failure in Children; Diagnostic Test: The Aristotle score; Other: Assessment of administered specific therapy; Diagnostic Test: Multispiral computed tomography/3D echocardiography; Diagnostic Test: Transthoracic and transesophageal echocardiography; Diagnostic Test: 12-lead electrocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death Rate
Patient's death due to various causes during the first 30 days after the surgery.
Measured: From baseline till 1 month after the surgery
Secondary outcomes (9)
Number of Participants with Repeat Aortic Valve Surgery
We will observe if a patient had an emergency for the repeat surgery on the aortic valve
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Aortic Valve Mean Gradient over 40 mmHg
We will register the cases when the mean gradient at the aortic valve will exceed 40 mmHg
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Aortic Insufficiency Stage 2-4
We will register the cases when the patients will be diagnosed with aortic insufficiency Stage 2-4
Measured: During the 5-6 years of the follow-up period since the surgery
Neo-aortic valve effective area less than 1.0 cm2/m2
We will register the cases when the effective area of the neo-aortic valve will be less than 1.0 cm2/m2
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Hemorrhage requiring surgery
We will register the patients diagnosed with a hemorrhage requiring surgery
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Acute Disorders of Cerebral Circulation
We will register the patients with acute disorders of cerebral circulation after the surgery
Measured: During the first 30 days after the surgery
Number of Participants with Acute Kidney Injury Stages 2 or 3
We will register the patients with acute kidney injury Stages 2 or 3, including those requiring renal replacement therapy
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants withAcute Coronary Syndrome
We will register the patients diagnosed with acute coronary syndrome
Measured: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Dysfunction of the Neo-valve Requiring Repeat Intervention
We will register the cases when patients are diagnosed with dysfunction of the neo-valve after the surgery and require repeated operation
Measured: During the 5-6 years of the follow-up period since the surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2019
- Study start18 Feb 2020
- Primary completionOct 2026 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve InsufficiencyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Medical Research Center for Children's Health, Russian Federation
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Dmitry V. Ryabtsev, PhD, Principal investigator, National Research Center of Children's Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04162444
- Sponsor's protocol ID
- 16072019
- Status last verified
- Mar 2021
- First submitted
- 11 Nov 2019
- Last updated
- 3 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data will be made available partially upon a request.
Publications
Salomon NW, Stinson EB, Oyer P, Copeland JG, Shumway NE. Operative treatment of congenital aortic stenosis. Ann Thorac Surg. 1978 Nov;26(5):452-60. doi: 10.1016/s0003-4975(10)62925-6.
PubMed 753159Brown JW, Ruzmetov M, Vijay P, Rodefeld MD, Turrentine MW. Surgery for aortic stenosis in children: a 40-year experience. Ann Thorac Surg. 2003 Nov;76(5):1398-411. doi: 10.1016/s0003-4975(03)01027-0.
PubMed 14602258Karamlou T, Jang K, Williams WG, Caldarone CA, Van Arsdell G, Coles JG, McCrindle BW. Outcomes and associated risk factors for aortic valve replacement in 160 children: a competing-risks analysis. Circulation. 2005 Nov 29;112(22):3462-9. doi: 10.1161/CIRCULATIONAHA.105.541649.
PubMed 16316968Alsoufi B. Aortic valve replacement in children: Options and outcomes. J Saudi Heart Assoc. 2014 Jan;26(1):33-41. doi: 10.1016/j.jsha.2013.11.003. Epub 2013 Nov 13.
PubMed 24578598Alsoufi B, Al-Halees Z, Manlhiot C, McCrindle BW, Al-Ahmadi M, Sallehuddin A, Canver CC, Bulbul Z, Joufan M, Fadel B. Mechanical valves versus the Ross procedure for aortic valve replacement in children: propensity-adjusted comparison of long-term outcomes. J Thorac Cardiovasc Surg. 2009 Feb;137(2):362-370.e9. doi: 10.1016/j.jtcvs.2008.10.010.
PubMed 19185153Ruzmetov M, Vijay P, Rodefeld MD, Turrentine MW, Brown JW. Evolution of aortic valve replacement in children: a single center experience. Int J Cardiol. 2006 Nov 10;113(2):194-200. doi: 10.1016/j.ijcard.2005.11.011. Epub 2006 Jan 10.
PubMed 16376439Alsoufi B, Manlhiot C, McCrindle BW, Canver CC, Sallehuddin A, Al-Oufi S, Joufan M, Al-Halees Z. Aortic and mitral valve replacement in children: is there any role for biologic and bioprosthetic substitutes? Eur J Cardiothorac Surg. 2009 Jul;36(1):84-90; discussion 90. doi: 10.1016/j.ejcts.2009.02.048. Epub 2009 Apr 14.
PubMed 19369085Polimenakos AC, Sathanandam S, Elzein C, Barth MJ, Higgins RS, Ilbawi MN. Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement. J Thorac Cardiovasc Surg. 2010 Apr;139(4):933-41; discussion 941. doi: 10.1016/j.jtcvs.2009.12.015.
PubMed 20304137Lupinetti FM, Duncan BW, Lewin M, Dyamenahalli U, Rosenthal GL. Comparison of autograft and allograft aortic valve replacement in children. J Thorac Cardiovasc Surg. 2003 Jul;126(1):240-6. doi: 10.1016/s0022-5223(03)00041-2.
PubMed 12878961Solowiejczyk DE, Bourlon F, Apfel HD, Hordof AJ, Hsu DT, Crabtree G, Galantowicz M, Gersony WM, Quaegebeur JM. Serial echocardiographic measurements of the pulmonary autograft in the aortic valve position after the Ross operation in a pediatric population using normal pulmonary artery dimensions as the reference standard. Am J Cardiol. 2000 May 1;85(9):1119-23. doi: 10.1016/s0002-9149(00)00707-4.
PubMed 10781763Elkins RC, Knott-Craig CJ, Ward KE, McCue C, Lane MM. Pulmonary autograft in children: realized growth potential. Ann Thorac Surg. 1994 Jun;57(6):1387-93; discussion 1393-4. doi: 10.1016/0003-4975(94)90089-2.
PubMed 8010778Solymar L, Sudow G, Holmgren D. Increase in size of the pulmonary autograft after the Ross operation in children: growth or dilation? J Thorac Cardiovasc Surg. 2000 Jan;119(1):4-9. doi: 10.1016/s0022-5223(00)70211-x.
PubMed 10612754Simon P, Aschauer C, Moidl R, Marx M, Keznickl FP, Eigenbauer E, Wolner E, Wollenek G. Growth of the pulmonary autograft after the Ross operation in childhood. Eur J Cardiothorac Surg. 2001 Feb;19(2):118-21. doi: 10.1016/s1010-7940(00)00638-2.
PubMed 11167098Hraska V, Krajci M, Haun Ch, Ntalakoura K, Razek V, Lacour-Gayet F, Weil J, Reichenspurner H. Ross and Ross-Konno procedure in children and adolescents: mid-term results. Eur J Cardiothorac Surg. 2004 May;25(5):742-7. doi: 10.1016/j.ejcts.2004.01.009.
PubMed 15082276Elkins RC, Thompson DM, Lane MM, Elkins CC, Peyton MD. Ross operation: 16-year experience. J Thorac Cardiovasc Surg. 2008 Sep;136(3):623-30, 630.e1-5. doi: 10.1016/j.jtcvs.2008.02.080.
PubMed 18805263
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-term and Midterm Results of the Aortic Valve Reconstruction With Autopericardium in Children
- ClinicalTrials.gov ID
- NCT04162444
- Acronym / sponsor ID
- 16072019
- Conditions
- Aortic Valve Insufficiency
- Keywords
- Aortic Valve Insufficiency/surgery, Aortic Valve/surgery, Child, Reconstructive Surgical Procedures/methods, Cardiac Surgical Procedures, Hemodynamics, Pericardium/transplantation, Transplantation, Autologous
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National Medical Research Center for Children's Health, Russian FederationOther government
- Study start
- 18 Feb 2020 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 14 Nov 2019 (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.
Aortic valve disease counts up to 5% of cases of congenital heart disease being one of the most common congenital malformations of the cardiovascular system. This disease requires replacement of the damaged valve which in itself is not a trivial task to complete in children as there is still no available best practice for valve replacement. Today, the following alternative variants are performed in children: mechanical aortic prosthesis, xenografts, allografts, and pulmonary autograft (Ross procedure) and each has its potential advantages and disadvantages.
Mechanical aortic prostheses require lifelong anticoagulation therapy and repeated surgeries to replace mechanical valves during child growth. Available xenografts in children also has suboptimal results not only because of absence of growth potential, but also due to development of degenerative changes in biological tissue of the graft leaflets. Allograft tissues are exposed to rapid biodegradation in the recipient body and thus requiring repeated surgeries associated with higher difficulty, high risk of hemorrhages, and injury of the coronary injuries. Ross procedure was proposed as theoretically the most evidence-based reconstruction of the aortic valve in children. Even successfully performed Ross operation transforms one-valve disorder into two-valve disease.
The accumulation of knowledge on the anatomy of the aortic root and improvement of surgical techniques led to the development of new methods for reconstruction of the valve function. The technique is widely applied in adult cardiac surgery, uses glutaraldehyde-treated autopericardium for augmentation of the leaflets. Absence of foreign material provides no need for anticoagulation therapy. Potentially, reconstruction of the aortic valve with autopericardium can be widely used in children.
Aim is to study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. Patients aged 29 days to 12 years will be included into the study. The data according to the protocol of the study will be assessed at the stage of inclusion, during the surgery, in 30 days after the surgery, and in 1, 2, and 3 years after the surgery. Data about all the patients included into the research will be analyzed in order to study the endpoints and achieve the research aim.
Detailed description
Aortic valve disease amounts to approximately 5% of the total number of cases of congenital heart disease, thus being one of the most common congenital malformations of the cardiovascular system. This disease requires replacement of the damaged valve, which in itself is not a trivial task to complete in children as there is still no available perfect option for valve replacement. Today, the following alternative variants for the aortic valve reconstruction in children are known: mechanical aortic prosthesis, xenografts, allografts and pulmonary autograft (Ross procedure); each of the above-mentioned variants has its potential advantages and disadvantages.
Mechanical aortic prostheses are widely available, including in small sizes (16 and 18 mm) appropriate for young children. However, the available sizes still do not allow to perform the surgical reconstruction in children of the first year of life. Besides these patients need lifelong anticoagulation therapy and necessity for repeated surgeries in order to replace mechanical valves with a child's growth.
Available xenografts have various types but usually, their sizes begin from 19 mm which does not fit for the majority of young children. Aortic xenografts are characterized by low risk of thromboembolism complications and do not require lifelong antithrombotic therapy. However, application of these grafts in children also has suboptimal results not only because of the absence of growth potential but also due to the development of degenerative changes in biological tissue of the graft leaflets.
Allografts are characterized by perfect hemodynamic parameters which are similar to the native healthy aortic valve. Risk of thromboembolic complications in implantation of allografts is very low, so there is no need for anticoagulation therapy. As in xenografts, allograft tissues are exposed to rapid biodegradation in the recipient body with the following development of obstruction or insufficiency and thus requiring a repeat operation. Implantation of allografts is associated with higher difficulty and high risk of hemorrhages and injury of the coronary injuries.
Ross procedure was proposed as theoretically the most justified choice for reconstruction of the aortic valve in children. As a conduit for reconstruction of the aortic valve the host's intact native pulmonary valve - autograft - is used; and the pulmonary valve is usually replaced by xenograft. Even successfully performed Ross operation, according to some authors, resolves the problem of the aortic valve only for a while; moreover, it causes another problem with the pulmonary valve, thus transforming one-valve disorder into two-valve disease.
The accumulation of knowledge on the anatomy of the aortic root and improvement of surgical techniques has led to the development of new methods for reconstruction of the valve function. The experience of various options for interventions on the aortic valve leaflet gained in adult cardiac surgery allowed to consider such interventions as an alternative method to valve reconstruction in children. About ten years ago, Professor Shigeyuki Ozaki brought the reconstruction of the aortic valve with the patient's own tissues to a completely new technological level. This technique includes the use of glutaraldehyde-treated autopericardium for augmentation of the leaflets; the reproducibility of the method was significantly increased due to usage of the template sets and special tools for the measurement of the native valve. Since no foreign material is used, there is no need for anticoagulation therapy after such intervention, which the authors of the method referred to as the valve reconstruction, not implantation of the graft. Potentially, reconstruction of the aortic valve with autopericardium can be widely used in children. In this population of patients, the various variants of the leaflets dysmorphogenesis are much more common, a wide range of morphological diversity of structure with inadequate hemodynamics can be found: monocuspid, bicuspid and pseudobicuspid valves; which does not allow to perform the valve reconstruction by restoring the original anatomy.
The normal anatomy of the aortic valve assumes three-valve structure, and most augmentation techniques suppose formation of tricuspid anatomy. At the same time, there is an alternative variant of hemodynamically adequate valve structure in the human body - bicuspid anatomy of the venous valves in the vena cava inferior system. Theoretical calculations obtained through computer simulation show that the neo-valve formed by three artificial leaflets will retain its locking function with increasing the diameter of the fibrous ring only by 8%. At the same time, the bicuspid valve with an increased height of the leaflets is able to maintain the shut-off function with an increase in the diameter of the fibrous ring by 67%.
The aim is to study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. Primary endpoints: patient's death due to various causes during the first 30 days after the surgery. Secondary endpoints for efficacy assessment: аreedom from repeated surgeries on the aortic valve; mean gradient at the aortic valve over 40 mmHg; аortic insufficiency over 2 degree; effective area of the neo-aortic valve less than 1.0 cm2/m2 Secondary endpoint for safety assessment: acute disorders of cerebral circulation within the first 30 days after the surgery; hemorrhage needing revision surgery; acute kidney injury, stages 2 or 3, including the necessity for renal replacement therapy; acute coronary syndrome; dysfunction of the neo-valve requiring repeated surgery.
Patients aged from 29 days to 12 years old with dysfunction of the native aortic valve with and without manifestations, with indications for the aortic valve reconstruction, and without concomitant supravalvular and subvalvular aortic stenosis and major congenital heart diseases, will be included into the study. The study design is planned to be prospective, cohort, single-center, observational. In total 40 patients will be included into the study. The data according to the protocol of the study will be assessed at the stage of inclusion, during the surgery, in 30 days after the surgery, and in 1, 2, and 3 years after the surgery. Data about all the patients included in the research will be analyzed in order to study the endpoints and achieve the research aim.
The first report on safety of the operation will be published when all the patients included in the study are carried out the procedure of augmentation of the aortic valve with autopericardium and all of them are examined within 30 days after the surgery. A report about the efficacy of the operation within the first year after the performed surgery of augmentation of the aortic valve with autopericardium; it will be published after all the patients included in the study are examined at the control visit in one year after the surgery. Report about clinical and hemodynamic efficacy of the operation within three years after the performed reconstruction of the aortic valve with autopericarduim; it will be published after all the patients included in the study are examined in three years after the surgery. Final report on the study will be published when for all patients included in the study all the follow-up periods are completed, or patients are excluded from the study due to other causes.
For compensation for the lost quantitative or qualitative data, statistical methods will not be applied. If there is a lack in patient's data due to any causes, such a patient will be excluded from this block of analysis. A number of patients included in each analysis will be represented in the report, so readers could themselves assess the influence of the lost data on the published result.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | Diagnostic Test: Physical examination, Diagnostic Test: The Ross Classification for Heart Failure in Children, Diagnostic Test: The Aristotle score, Other: Assessment of administered specific therapy, Diagnostic Test: Multispiral computed tomography/3D echocardiography, Diagnostic Test: Transthoracic and transesophageal echocardiography, Diagnostic Test: 12-lead electrocardiogramWe will study safety, clinical and hemodynamic efficacy of the method of the aortic valve reconstruction with autopericardium in children with aortic valve disease. |
Who may qualify
- Ages
- 29 days to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study will enroll the participants from the patients of the the Department of Cardiac Surgery with dysfunction of the native aortic valve with and without manifestations, with indications for the aortic valve reconstruction, and without concomitant supravalvular and subvalvular aortic stenosis and major congenital heart diseases.
Key inclusion criteria (16 listed)
- Age from 29 days to 12 years
- Patient's official caregivers have to sign the informed consent after they are thoroughly explained the meaning of the study, its protocol and timelines.
- Patients with manifestations, with mean gradient at the aortic valve >40 mmHg with normal left ventricular ejection fraction (LVEF), or patients with manifestations with the mean gradient < 40 mmHg with decreased LVEF, or patients with manifestations with severe aortic insufficiency, or patients without manifestations, but with decreased LVEF with aortic insufficiency, or patients with concomitant moderate aortic insufficiency and moderate aortic stenosis with manifestations.
- Aortic Z-score over -1,5
- Absence of subvalvular and supravalvular aortic stenosis
Key exclusion criteria (1 listed)
- Refusal of patient's caregivers to participate further in the study.
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 |
|---|---|---|
| Physical examinationAlso: Medical examination, Clinical examinationA physical examination is a routine screening procedure used to investigate a patient's symptoms or complaints. It consists of a series of questions regarding patient medical history followed by an examination of the symptoms to determine the correct diagnosis and treatment plan. | Diagnostic test | Cohort 1 |
| The Ross Classification for Heart Failure in ChildrenAlso: Assessment of heart failure according to Ross scaleThe assessment is performed by pediatric cardiologist according to the classic Ross scale. One of the 4 classes of chronic heart failure is registered. | Diagnostic test | Cohort 1 |
| The Aristotle scoreAlso: Assessment of surgical risks according to the ARISTOTLE scoreSurgical risks will be assessed by the ARISTOTLE score developed specially for the task. The calculation will be performed online, available from http://www.aristotleinstitute.org. | Diagnostic test | Cohort 1 |
| Assessment of administered specific therapyThe data will be registered as groups of administered medicines: * Antiplatelet agents * Loop diuretics * Potassium-sparing diuretics * Angiotensin-converting enzyme inhibitors | Other | Cohort 1 |
| Multispiral computed tomography/3D echocardiographyAlso: MS-CT/3D-echoAll patients enrolled in the study should be routinely examined with multispiral computed tomography (MS-CT) or 3D-echo before surgery and 3 years later. As a result, a 3D aortic root reconstruction will be made to assess its size and anatomy and subsequently build a 3D soft model for surgery imitation. At the study onset, we plan to perform MS-CT, then 3D-echo. If the correlation resulting from 3D-echo and the actual sizes will be high, the isolated 3D-echo will be preferred in the future. If none of the methods is available, the patients will not be enrolled in the study. The following data will be registered for further analysis: * Perimeter of the aortic valve * Diameter of the aortic valve at sinuses level * Height of the aortic sinuses * Morphology of the aortic valve | Diagnostic test | Cohort 1 |
| Transthoracic and transesophageal echocardiographyTransthoracic echocardiography is carried out at baseline, at discharge and then annually. It is performed in order to assess the contractile function of the heart and hemodynamic characteristics of the aortic valve and its autopericardium graft. Transesophageal echocardiography is carried out directly after the withdrawal of the artificial circulation when performing augmentation of the aortic valve with autopericardium in order to asses hemodynamic characteristics of the aortic neo-valve. | Diagnostic test | Cohort 1 |
| 12-lead electrocardiogramAlso: 12-lead ECGRegistering 12-lead electrocardiogram (ECG) is used as a tool for assessment of the regularity of the heart rhythm as well as screening and predictive tool for assessment of fibrosis and hypertrophy processes in the myocardium. The following data will be registered: * Heart rate * Sinus rhythm (yes/no) * Positive R wave in leads V5-6 * Angle α less than 0 * Presence/absence of abnormal Q wave * Presence/absence of ST-segment depression in precordial leads | Diagnostic test | Cohort 1 |
Primary outcome
Death Rate
Time frame: From baseline till 1 month after the surgery
Patient's death due to various causes during the first 30 days after the surgery.
9 secondary outcomes
Number of Participants with Repeat Aortic Valve Surgery
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Aortic Valve Mean Gradient over 40 mmHg
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Aortic Insufficiency Stage 2-4
Time frame: During the 5-6 years of the follow-up period since the surgery
Neo-aortic valve effective area less than 1.0 cm2/m2
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Hemorrhage requiring surgery
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Acute Disorders of Cerebral Circulation
Time frame: During the first 30 days after the surgery
Number of Participants with Acute Kidney Injury Stages 2 or 3
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants withAcute Coronary Syndrome
Time frame: During the 5-6 years of the follow-up period since the surgery
Number of Participants with Dysfunction of the Neo-valve Requiring Repeat Intervention
Time frame: During the 5-6 years of the follow-up period since the 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 3 Mar 2021.
- Results publication: PubMed 753159Salomon NW, Stinson EB, Oyer P, Copeland JG, Shumway NE. Operative treatment of congenital aortic stenosis. Ann Thorac Surg. 1978 Nov;26(5):452-60. doi: 10.1016/s0003-4975(10)62925-6.
- Results publication: PubMed 14602258Brown JW, Ruzmetov M, Vijay P, Rodefeld MD, Turrentine MW. Surgery for aortic stenosis in children: a 40-year experience. Ann Thorac Surg. 2003 Nov;76(5):1398-411. doi: 10.1016/s0003-4975(03)01027-0.
- Results publication: PubMed 16316968Karamlou T, Jang K, Williams WG, Caldarone CA, Van Arsdell G, Coles JG, McCrindle BW. Outcomes and associated risk factors for aortic valve replacement in 160 children: a competing-risks analysis. Circulation. 2005 Nov 29;112(22):3462-9. doi: 10.1161/CIRCULATIONAHA.105.541649.
- Results publication: PubMed 24578598Alsoufi B. Aortic valve replacement in children: Options and outcomes. J Saudi Heart Assoc. 2014 Jan;26(1):33-41. doi: 10.1016/j.jsha.2013.11.003. Epub 2013 Nov 13.
- Results publication: PubMed 19185153Alsoufi B, Al-Halees Z, Manlhiot C, McCrindle BW, Al-Ahmadi M, Sallehuddin A, Canver CC, Bulbul Z, Joufan M, Fadel B. Mechanical valves versus the Ross procedure for aortic valve replacement in children: propensity-adjusted comparison of long-term outcomes. J Thorac Cardiovasc Surg. 2009 Feb;137(2):362-370.e9. doi: 10.1016/j.jtcvs.2008.10.010.
- Results publication: PubMed 16376439Ruzmetov M, Vijay P, Rodefeld MD, Turrentine MW, Brown JW. Evolution of aortic valve replacement in children: a single center experience. Int J Cardiol. 2006 Nov 10;113(2):194-200. doi: 10.1016/j.ijcard.2005.11.011. Epub 2006 Jan 10.
- Results publication: PubMed 19369085Alsoufi B, Manlhiot C, McCrindle BW, Canver CC, Sallehuddin A, Al-Oufi S, Joufan M, Al-Halees Z. Aortic and mitral valve replacement in children: is there any role for biologic and bioprosthetic substitutes? Eur J Cardiothorac Surg. 2009 Jul;36(1):84-90; discussion 90. doi: 10.1016/j.ejcts.2009.02.048. Epub 2009 Apr 14.
- Results publication: PubMed 20304137Polimenakos AC, Sathanandam S, Elzein C, Barth MJ, Higgins RS, Ilbawi MN. Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement. J Thorac Cardiovasc Surg. 2010 Apr;139(4):933-41; discussion 941. doi: 10.1016/j.jtcvs.2009.12.015.
- Results publication: PubMed 12878961Lupinetti FM, Duncan BW, Lewin M, Dyamenahalli U, Rosenthal GL. Comparison of autograft and allograft aortic valve replacement in children. J Thorac Cardiovasc Surg. 2003 Jul;126(1):240-6. doi: 10.1016/s0022-5223(03)00041-2.
- Results publication: PubMed 10781763Solowiejczyk DE, Bourlon F, Apfel HD, Hordof AJ, Hsu DT, Crabtree G, Galantowicz M, Gersony WM, Quaegebeur JM. Serial echocardiographic measurements of the pulmonary autograft in the aortic valve position after the Ross operation in a pediatric population using normal pulmonary artery dimensions as the reference standard. Am J Cardiol. 2000 May 1;85(9):1119-23. doi: 10.1016/s0002-9149(00)00707-4.
- Results publication: PubMed 8010778Elkins RC, Knott-Craig CJ, Ward KE, McCue C, Lane MM. Pulmonary autograft in children: realized growth potential. Ann Thorac Surg. 1994 Jun;57(6):1387-93; discussion 1393-4. doi: 10.1016/0003-4975(94)90089-2.
- Results publication: PubMed 10612754Solymar L, Sudow G, Holmgren D. Increase in size of the pulmonary autograft after the Ross operation in children: growth or dilation? J Thorac Cardiovasc Surg. 2000 Jan;119(1):4-9. doi: 10.1016/s0022-5223(00)70211-x.
- Dhand NK, Khatkar MS. (2014). Statulator: an online statistical calculator. Sample Size Calculator for Estimating a Single Proportion. Accessed 15 March 2019Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be made available partially upon a request.
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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.
Dmitry V. Ryabtsev, PhD principal investigator
National Research Center of Children's Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Valve Insufficiency, run by National Medical Research Center for Children's Health, Russian Federation at 1 site in Russia.
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 16 inclusion and 1 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 3 Mar 2021. 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 Russia. 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 Vladimir P. Miroshnichenko, PhD (+7 499 134-04-70, miroshnichenko@nczd.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death Rate (time frame: From baseline till 1 month after the surgery). 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 NCT04162444, which also lists 36 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 3 Mar 2021.