Cardiovascular DiseasesPhase 3BCASNCT00000470
Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
A Phase 3 study testing cardiac surgical procedures and cardiopulmonary bypass in people with Cardiovascular Diseases and Cerebral Anoxia, run by Boston Children's Hospital.
Trial summary
To compare the influence of two surgical anesthetic techniques, hypothermia with circulatory arrest or hypothermia with low-flow bypass perfusion, on neurologic functioning in infants undergoing heart surgery. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Cardiovascular Diseases, Cerebral Anoxia, Cerebrovascular Disorders
- What is being tested?
- cardiac surgical procedures and cardiopulmonary bypass
- Type of treatment
- Surgery or procedure
- How many people
- 171 participants
- Where
- No sites listed yet
- Study dates
- Dec 1988to Oct 1993
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 1 year
- All sexes
- No healthy volunteers
- Child
Boy and girl infants, up to three months of age, with transposition of the great arteries with or without septal defect.
About this study
To compare the influence of two surgical anesthetic techniques, hypothermia with circulatory arrest or hypothermia with low-flow bypass perfusion, on neurologic functioning in infants undergoing heart surgery.
Read the detailed description
BACKGROUND:
The pediatric medical community has long been concerned about the increased incidence of cerebral dysfunction among newborns with severe cyanotic congenital heart disease. There has been concern about a great number of potential predisposing factors including the effects of hypoxemia and acidosis, trauma during cardiac catheterization, and the duration of prolonged decreased arterial oxygen saturation. Many infants undoubtedly undergo significant brain damage prior to surgery, but may be subject to further insult in the peri-operative period. The proposed trial studied circulatory arrest versus low-flow bypass methods of surgical support in a homogeneous group of patients who were managed in identical fashion in all other aspects of their treatment. Major factors, such as the influence of cardiac catheterization and presurgical status were specifically incorporated into the primary statistical analysis. This was important in order to identify significant predisposing causes of brain injury beyond the surgical techniques being compared, and to increase the power of the comparison.
DESIGN NARRATIVE:
Randomized, partially blinded. Infants were assigned to deep hypothermia and either circulatory arrest or low-flow bypass support during arterial switch surgical repair of transposition of the great arteries. Randomization was stratified by diagnosis (with or without septal defect) and by specific surgeon of three, thus yielding six strata within each treatment group. Randomization was also blocked to minimize imbalances in treatment assignment between strata. The study was partially blinded, in that outcome data were obtained by investigators who were unaware of management, surgical care, and intensive care were standardized. Hemodynamic assessment was made early in the post-operative period. The outcomes of primary interest (magnetic resonance imaging, neurologic examination, and psychometric testing) were reviewed at the one-year evaluation, to maximize relevance to the long-term prognosis. Pre-operative and seven-to-ten day post-operative neurologic examination was also carried out. Developmental status at one year was measured by the Bayley developmental scales and the Fagan test of infant intelligence. Brain function was assessed by neurologic examination at one year. The recruitment period extended from April 1988 to February 1992.
The trial was extended through December 1997 to allow four years of follow-up. The follow-up allowed the assessment of a primary outcome variable in the neurologic domain and a primary outcome variable in the developmental domain. The primary outcome variable of the neurologic examination resulted in an ordered classification of three categories of normal, minor, and major dysfunction, such as apraxia or cerebral palsy. Development was assessed using standardized measures of cognition, behavior, language, attention, and motor skills. The primary outome variable for the developmental evaluation was the intelligence quotient on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). Secondary outcome variables included measurements of behavior and performance in specific domains of speech and language, visual motor integration, attention, motor function, and temperament.
Beginning in January 1998, the study was extended for an additional four years through December 2001 to compare the effects of the two intraoperative methods with respect to developmental and neurologic status at eight years of age. Developmental status was assessed by the Wechsler Individual Achievement Test (primary outcome) and by the presence of learning disabilities and performance in specific neuropsychologic domains (secondary outcomes). Neurologic status was determined by neurologic exam (primary outcome) and by specific types of dysfunction such as motor problems. The study also compared the academic and intellectual performance of the cohort at age eight years to population norms and used the data to identify correlates of the children's eight year outcomes, as well as their development between ages one and eight.
- Conditions
- Cardiovascular Diseases, Cerebral Anoxia, Cerebrovascular Disorders, Defect, Congenital Heart, Heart Diseases, Transposition of Great Vessels
- Being tested
- cardiac surgical procedures, cardiopulmonary bypass
- Medical subject headings
- Cardiovascular Diseases, Hypoxia, Brain, Cerebrovascular Disorders, Heart Defects, Congenital, Heart Diseases, Transposition of Great Vessels, Heart Septal Defects, Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cardiac surgical proceduresProcedure or surgery
cardiopulmonary bypassProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startDec 1988
- Primary completionFeb 1992
- Study completionOct 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jane W. Newburger, Boston Children's Hospital
- Investigators
- Jane Newburger, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000470
- Sponsor's protocol ID
- 59
- Other IDs
- R01HL041786
- Acronym
- BCAS
- Status last verified
- Jul 2016
- First submitted
- 27 Oct 1999
- Last updated
- 29 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Not required when trial was performed in 1988-92
Publications
Jonas RA. Hypothermia, circulatory arrest, and the pediatric brain. J Cardiothorac Vasc Anesth. 1996 Jan;10(1):66-74. doi: 10.1016/s1053-0770(96)80180-7.
PubMed 8634389Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. doi: 10.1161/01.cir.92.8.2226.
PubMed 7554206Wernovsky G, Jonas RA, Colan SD, Sanders SP, Wessel DL, Castanneda AR, Mayer JE Jr. Results of the arterial switch operation in patients with transposition of the great arteries and abnormalities of the mitral valve or left ventricular outflow tract. J Am Coll Cardiol. 1990 Nov;16(6):1446-54. doi: 10.1016/0735-1097(90)90391-2.
PubMed 2229800Chang AC, Wernovsky G, Kulik TJ, Jonas RA, Wessel DL. Management of the neonate with transposition of the great arteries and persistent pulmonary hypertension. Am J Cardiol. 1991 Nov 1;68(11):1253-5. doi: 10.1016/0002-9149(91)90209-4. No abstract available.
PubMed 1951094Jenkins KJ, Hanley FL, Colan SD, Mayer JE Jr, Castaneda AR, Wernovsky G. Function of the anatomic pulmonary valve in the systemic circulation. Circulation. 1991 Nov;84(5 Suppl):III173-9.
PubMed 1718628Bellinger DC, Wernovsky G, Rappaport LA, Mayer JE Jr, Castaneda AR, Farrell DM, Wessel DL, Lang P, Hickey PR, Jonas RA, et al. Cognitive development of children following early repair of transposition of the great arteries using deep hypothermic circulatory arrest. Pediatrics. 1991 May;87(5):701-7.
PubMed 2020517Wernovsky G, Giglia TM, Jonas RA, Mone SM, Colan SD, Wessel DL. Course in the intensive care unit after 'preparatory' pulmonary artery banding and aortopulmonary shunt placement for transposition of the great arteries with low left ventricular pressure. Circulation. 1992 Nov;86(5 Suppl):II133-9.
PubMed 1385008Wernovsky G, Bridges ND, Mandell VS, Castaneda AR, Perry SB. Enlarged bronchial arteries after early repair of transposition of the great arteries. J Am Coll Cardiol. 1993 Feb;21(2):465-70. doi: 10.1016/0735-1097(93)90690-3.
PubMed 8426012Newburger JW, Jonas RA, Wernovsky G, Wypij D, Hickey PR, Kuban KC, Farrell DM, Holmes GL, Helmers SL, Constantinou J, Carrazana E, Barlow JK, Walsh AZ, Lucius KC, Share JC, Wessel DL, Hanley FL, Mayer JE, Costaneda AR, Ware JH, et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med. 1993 Oct 7;329(15):1057-64. doi: 10.1056/NEJM199310073291501.
PubMed 8371727Jonas RA, Bellinger DC, Rappaport LA, Wernovsky G, Hickey PR, Farrell DM, Newburger JW. Relation of pH strategy and developmental outcome after hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1993 Aug;106(2):362-8.
PubMed 8341077Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995 Mar 2;332(9):549-55. doi: 10.1056/NEJM199503023320901.
PubMed 7838188Wernovsky G, Mayer JE Jr, Jonas RA, Hanley FL, Blackstone EH, Kirklin JW, Castaneda AR. Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg. 1995 Feb;109(2):289-301; discussion 301-2. doi: 10.1016/S0022-5223(95)70391-8.
PubMed 7853882Rhodes LA, Wernovsky G, Keane JF, Mayer JE Jr, Shuren A, Dindy C, Colan SD, Walsh EP. Arrhythmias and intracardiac conduction after the arterial switch operation. J Thorac Cardiovasc Surg. 1995 Feb;109(2):303-10. doi: 10.1016/S0022-5223(95)70392-6.
PubMed 7853883Weindling SN, Wernovsky G, Colan SD, Parker JA, Boutin C, Mone SM, Costello J, Castaneda AR, Treves ST. Myocardial perfusion, function and exercise tolerance after the arterial switch operation. J Am Coll Cardiol. 1994 Feb;23(2):424-33. doi: 10.1016/0735-1097(94)90430-8.
PubMed 8294697Kupferschmid JP, Burns SA, Jonas RA, Keane JF, Spevak PJ, Wernovsky G. Repair of double aortic arch associated with D-transposition of the great arteries. Ann Thorac Surg. 1993 Sep;56(3):570-2. doi: 10.1016/0003-4975(93)90905-w.
PubMed 8379738
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
- ClinicalTrials.gov ID
- NCT00000470
- Acronym / sponsor ID
- BCAS / 59
- Conditions
- Cardiovascular Diseases, Cerebral Anoxia, Cerebrovascular Disorders, Defect, Congenital Heart, Heart Diseases, Transposition of Great Vessels
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 1988
- Primary completion
- Feb 1992 (actual)
- Study completion
- Oct 1993 (actual)
- First posted
- 28 Oct 1999 (estimated)
- 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.
To compare the influence of two surgical anesthetic techniques, hypothermia with circulatory arrest or hypothermia with low-flow bypass perfusion, on neurologic functioning in infants undergoing heart surgery.
Detailed description
BACKGROUND:
The pediatric medical community has long been concerned about the increased incidence of cerebral dysfunction among newborns with severe cyanotic congenital heart disease. There has been concern about a great number of potential predisposing factors including the effects of hypoxemia and acidosis, trauma during cardiac catheterization, and the duration of prolonged decreased arterial oxygen saturation. Many infants undoubtedly undergo significant brain damage prior to surgery, but may be subject to further insult in the peri-operative period. The proposed trial studied circulatory arrest versus low-flow bypass methods of surgical support in a homogeneous group of patients who were managed in identical fashion in all other aspects of their treatment. Major factors, such as the influence of cardiac catheterization and presurgical status were specifically incorporated into the primary statistical analysis. This was important in order to identify significant predisposing causes of brain injury beyond the surgical techniques being compared, and to increase the power of the comparison.
DESIGN NARRATIVE:
Randomized, partially blinded. Infants were assigned to deep hypothermia and either circulatory arrest or low-flow bypass support during arterial switch surgical repair of transposition of the great arteries. Randomization was stratified by diagnosis (with or without septal defect) and by specific surgeon of three, thus yielding six strata within each treatment group. Randomization was also blocked to minimize imbalances in treatment assignment between strata. The study was partially blinded, in that outcome data were obtained by investigators who were unaware of management, surgical care, and intensive care were standardized. Hemodynamic assessment was made early in the post-operative period. The outcomes of primary interest (magnetic resonance imaging, neurologic examination, and psychometric testing) were reviewed at the one-year evaluation, to maximize relevance to the long-term prognosis. Pre-operative and seven-to-ten day post-operative neurologic examination was also carried out. Developmental status at one year was measured by the Bayley developmental scales and the Fagan test of infant intelligence. Brain function was assessed by neurologic examination at one year. The recruitment period extended from April 1988 to February 1992.
The trial was extended through December 1997 to allow four years of follow-up. The follow-up allowed the assessment of a primary outcome variable in the neurologic domain and a primary outcome variable in the developmental domain. The primary outcome variable of the neurologic examination resulted in an ordered classification of three categories of normal, minor, and major dysfunction, such as apraxia or cerebral palsy. Development was assessed using standardized measures of cognition, behavior, language, attention, and motor skills. The primary outome variable for the developmental evaluation was the intelligence quotient on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). Secondary outcome variables included measurements of behavior and performance in specific domains of speech and language, visual motor integration, attention, motor function, and temperament.
Beginning in January 1998, the study was extended for an additional four years through December 2001 to compare the effects of the two intraoperative methods with respect to developmental and neurologic status at eight years of age. Developmental status was assessed by the Wechsler Individual Achievement Test (primary outcome) and by the presence of learning disabilities and performance in specific neuropsychologic domains (secondary outcomes). Neurologic status was determined by neurologic exam (primary outcome) and by specific types of dysfunction such as motor problems. The study also compared the academic and intellectual performance of the cohort at age eight years to population norms and used the data to identify correlates of the children's eight year outcomes, as well as their development between ages one and eight.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 |
|---|---|---|
| cardiac surgical procedures | Procedure or surgery | – |
| cardiopulmonary bypass | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2016.
- Background: PubMed 8634389Jonas RA. Hypothermia, circulatory arrest, and the pediatric brain. J Cardiothorac Vasc Anesth. 1996 Jan;10(1):66-74. doi: 10.1016/s1053-0770(96)80180-7.
- Background: PubMed 7554206Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. doi: 10.1161/01.cir.92.8.2226.
- Background: PubMed 2229800Wernovsky G, Jonas RA, Colan SD, Sanders SP, Wessel DL, Castanneda AR, Mayer JE Jr. Results of the arterial switch operation in patients with transposition of the great arteries and abnormalities of the mitral valve or left ventricular outflow tract. J Am Coll Cardiol. 1990 Nov;16(6):1446-54. doi: 10.1016/0735-1097(90)90391-2.
- Background: PubMed 1951094Chang AC, Wernovsky G, Kulik TJ, Jonas RA, Wessel DL. Management of the neonate with transposition of the great arteries and persistent pulmonary hypertension. Am J Cardiol. 1991 Nov 1;68(11):1253-5. doi: 10.1016/0002-9149(91)90209-4. No abstract available.
- Background: PubMed 1718628Jenkins KJ, Hanley FL, Colan SD, Mayer JE Jr, Castaneda AR, Wernovsky G. Function of the anatomic pulmonary valve in the systemic circulation. Circulation. 1991 Nov;84(5 Suppl):III173-9.
- Background: PubMed 2020517Bellinger DC, Wernovsky G, Rappaport LA, Mayer JE Jr, Castaneda AR, Farrell DM, Wessel DL, Lang P, Hickey PR, Jonas RA, et al. Cognitive development of children following early repair of transposition of the great arteries using deep hypothermic circulatory arrest. Pediatrics. 1991 May;87(5):701-7.
- Background: PubMed 1385008Wernovsky G, Giglia TM, Jonas RA, Mone SM, Colan SD, Wessel DL. Course in the intensive care unit after 'preparatory' pulmonary artery banding and aortopulmonary shunt placement for transposition of the great arteries with low left ventricular pressure. Circulation. 1992 Nov;86(5 Suppl):II133-9.
- Background: PubMed 8426012Wernovsky G, Bridges ND, Mandell VS, Castaneda AR, Perry SB. Enlarged bronchial arteries after early repair of transposition of the great arteries. J Am Coll Cardiol. 1993 Feb;21(2):465-70. doi: 10.1016/0735-1097(93)90690-3.
- Background: PubMed 8371727Newburger JW, Jonas RA, Wernovsky G, Wypij D, Hickey PR, Kuban KC, Farrell DM, Holmes GL, Helmers SL, Constantinou J, Carrazana E, Barlow JK, Walsh AZ, Lucius KC, Share JC, Wessel DL, Hanley FL, Mayer JE, Costaneda AR, Ware JH, et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med. 1993 Oct 7;329(15):1057-64. doi: 10.1056/NEJM199310073291501.
- Background: PubMed 8341077Jonas RA, Bellinger DC, Rappaport LA, Wernovsky G, Hickey PR, Farrell DM, Newburger JW. Relation of pH strategy and developmental outcome after hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1993 Aug;106(2):362-8.
- Background: PubMed 7838188Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995 Mar 2;332(9):549-55. doi: 10.1056/NEJM199503023320901.
- Background: PubMed 7853882Wernovsky G, Mayer JE Jr, Jonas RA, Hanley FL, Blackstone EH, Kirklin JW, Castaneda AR. Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg. 1995 Feb;109(2):289-301; discussion 301-2. doi: 10.1016/S0022-5223(95)70391-8.
- Individual participant dataSharing planned: No. Not required when trial was performed in 1988-92
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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. This study is not recruiting at the moment.
Jane Newburger
Children's Hospital Medical Center, Cincinnati
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cardiac surgical procedures and cardiopulmonary bypass in people with Cardiovascular Diseases and Cerebral Anoxia, run by Boston Children's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 29 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000470, which also lists 35 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 29 Jul 2016.