Cardiovascular DiseasesPhase 3NCT00006183
Comparison of Hematocrit Levels in Infant Heart Surgery
A Phase 3 study testing Cardiopulmonary Bypass with Two Different Intra-Operative Hematocrits and Thoracic Surgery in people with Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
The purpose of this study is to compare the effects of diluted hematocrit (HCT) levels of 35% versus 25% during hypothermic cardiopulmonary bypass (CPB) in infants with d-transposition of the great arteries, a malformation of the heart vessels. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital
- What is being tested?
- Cardiopulmonary Bypass with Two Different Intra-Operative Hematocrits and Thoracic Surgery
- Type of treatment
- Surgery or procedure
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to Jul 2005
- 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
Who may be able to join
- Undergoing repair of ventricular septal defect within 9 months of study entry
- Tetralogy of fallot
- D-transposition of the great arteries
- Atrio-ventricular septal defect
Who cannot join
- Birth weight less than 2.3 kg
- Recognizable phenotypic syndrome of congenital anomalies
- Extracardiac anomalies of greater than minor severity
- Previous cardiac surgery
- Associated cardiovascular anomalies requiring aortic arch reconstruction or additional open surgical procedures before the planned developmental follow-up
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hematocrit Strategy in Infant Heart Surgery
The purpose of this study is to compare the effects of diluted hematocrit (HCT) levels of 35% versus 25% during hypothermic cardiopulmonary bypass (CPB) in infants with d-transposition of the great arteries, a malformation of the heart vessels.
Read the detailed description
BACKGROUND:
The optimal degree of hemodilution during profoundly hypothermic CPB remains controversial, and widely dissimilar hemodilution studies have evolved at centers that perform infant cardiac surgery. HCT, a measurement of the volume of red blood cells, is of interest in cardiopulmonary bypass. Higher HCT levels expose individuals to the risks of microvascular occlusion (blockage in the small blood vessels), while lower HCT levels may critically limit oxygen delivery to the brain and other organs. Preliminary research suggests that higher HCT levels provide superior brain and myocardial protection, but there have not been any studies that report on outcomes after usage of higher versus lower HCT levels.
DESIGN NARRATIVE:
In this single-center, prospective, randomized study, hemodilution to a HCT level of 35% versus 25% will be compared with respect to neurodevelopmental outcome and early postoperative course in infants with congenital heart disease. The first aim of this study will test the hypothesis that hemodilution to a HCT level of 35%, compared to a level of 25%, will be associated with superior central nervous system protection. The primary outcome variable will be developmental outcome at age 1 year, assessed using the Bayley Scales of Infant Development. Secondary outcome variables include the following: 1) tissue release of S-100 protein as a measure of cerebral cellular injury; 2) cerebral hemodynamics and oxygenation, determined by near infrared spectroscopy (NIRS); 3) intrinsic cerebral vasoregulation, measured by NIRS and transcranial Doppler; and 4) at age 1 year, neurologic examination, the MacArthur inventory, and structural and volumetric findings of magnetic resonance imaging (MRI).
The second aim of this study will test the hypothesis that hemodilution to a HCT level of 35%, compared to a level of 25%, will be associated with better early postoperative cardiovascular status. The primary outcome measure will be serum lactate levels 1 hour after the surgery. Secondary outcome measures will include the following: 1) the duration of postoperative endotracheal intubation, ICU stay, and hospital stay; 2) serum lactate levels; 3) the PaO2/FiO2 ratio; 4) levels of circulating pro-inflammatory cytokines; and 5) the percent change in total body water, estimated by bioelectrical impedance. The structure of the study will allow assessment of whether 1-year outcomes can be predicted by perioperative variables other than the HCT strategies. Through the use of novel techniques such as NIRS and volumetric MRI, the study may also provide insight into mechanisms by which HCT and other perioperative variables affect the brain. The information obtained from this study should be broadly generalized to infants with other forms of congenital heart disease undergoing early repair and should have substantial impact on clinical practice.
- Conditions
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital, Transposition of Great Vessels
- Being tested
- Cardiopulmonary Bypass with Two Different Intra-Operative Hematocrits, Thoracic Surgery
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital, Transposition of Great Vessels
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiopulmonary Bypass with Two Different Intra-Operative HematocritsProcedure or surgery
Thoracic SurgeryProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum lactate levels (measured 1 hour after surgery)
Developmental outcome (measured by Bayley Scales of Infant Development at age 1 year)
Secondary outcomes (8)
Duration of postoperative endotracheal intubation, ICU stay, and hospital stay
PaO2/FiO2 ratio
Levels of circulating pro-inflammatory cytokines
Percent change in total body water, as estimated by bioelectrical impedance (measured 1 hour after surgery)
Tissue release of S-100 protein as a measure of cerebral cellular injury
Cerebral hemodynamics and oxygenation, as determined by near infrared spectroscopy (NIRS)
Intrinsic cerebral vasoregulation, as measured by NIRS and transcranial Doppler
Neurologic factors, as determined by neurologic examination, the MacArthur inventory, and structural and volumetric findings of MRI (measured at age 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2000 (estimated)
- Study startJul 2000
- Primary completionJul 2005
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)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 National Heart, Lung, and Blood Institute (NHLBI)The 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
- 120 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Jane W. Newburger, MD, MPH, Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006183
- Sponsor's protocol ID
- 131
- Other IDs
- U01HL063411
- Status last verified
- Mar 2008
- First submitted
- 21 Aug 2000
- Last updated
- 29 Jul 2016
- Results posted
- No
Publications
Jonas RA, Wypij D, Roth SJ, Bellinger DC, Visconti KJ, du Plessis AJ, Goodkin H, Laussen PC, Farrell DM, Bartlett J, McGrath E, Rappaport LJ, Bacha EA, Forbess JM, del Nido PJ, Mayer JE Jr, Newburger JW. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg. 2003 Dec;126(6):1765-74. doi: 10.1016/j.jtcvs.2003.04.003.
PubMed 14688685Bassan H, Gauvreau K, Newburger JW, Tsuji M, Limperopoulos C, Soul JS, Walter G, Laussen PC, Jonas RA, du Plessis AJ. Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery. Pediatr Res. 2005 Jan;57(1):35-41. doi: 10.1203/01.PDR.0000147576.84092.F9. Epub 2004 Nov 5.
PubMed 15531739Kussman BD, Wypij D, DiNardo JA, Newburger J, Jonas RA, Bartlett J, McGrath E, Laussen PC. An evaluation of bilateral monitoring of cerebral oxygen saturation during pediatric cardiac surgery. Anesth Analg. 2005 Nov;101(5):1294-1300. doi: 10.1213/01.ANE.0000180205.85490.85.
PubMed 16243983Rollins CK, Asaro LA, Akhondi-Asl A, Kussman BD, Rivkin MJ, Bellinger DC, Warfield SK, Wypij D, Newburger JW, Soul JS. White Matter Volume Predicts Language Development in Congenital Heart Disease. J Pediatr. 2017 Feb;181:42-48.e2. doi: 10.1016/j.jpeds.2016.09.070. Epub 2016 Nov 9.
PubMed 27837950Kussman BD, Wypij D, Laussen PC, Soul JS, Bellinger DC, DiNardo JA, Robertson R, Pigula FA, Jonas RA, Newburger JW. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010 Jul 20;122(3):245-54. doi: 10.1161/CIRCULATIONAHA.109.902338. Epub 2010 Jul 6.
PubMed 20606124Kipps AK, Wypij D, Thiagarajan RR, Bacha EA, Newburger JW. Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery. Pediatr Crit Care Med. 2011 Jan;12(1):52-6. doi: 10.1097/PCC.0b013e3181e30d43.
PubMed 20453699Soul JS, Robertson RL, Wypij D, Bellinger DC, Visconti KJ, du Plessis AJ, Kussman BD, Scoppettuolo LA, Pigula F, Jonas RA, Newburger JW. Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease. J Thorac Cardiovasc Surg. 2009 Aug;138(2):374-81. doi: 10.1016/j.jtcvs.2009.02.027. Epub 2009 Apr 10.
PubMed 19619781Newburger JW, Jonas RA, Soul J, Kussman BD, Bellinger DC, Laussen PC, Robertson R, Mayer JE Jr, del Nido PJ, Bacha EA, Forbess JM, Pigula F, Roth SJ, Visconti KJ, du Plessis AJ, Farrell DM, McGrath E, Rappaport LA, Wypij D. Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery. J Thorac Cardiovasc Surg. 2008 Feb;135(2):347-54, 354.e1-4. doi: 10.1016/j.jtcvs.2007.01.051.
PubMed 18242267
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
- Hematocrit Strategy in Infant Heart Surgery
- ClinicalTrials.gov ID
- NCT00006183
- Acronym / sponsor ID
- 131
- Conditions
- Cardiovascular Diseases, Heart Diseases, Heart Defects, Congenital, Transposition of Great Vessels
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jul 2000
- Primary completion
- Jul 2005 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 22 Aug 2000 (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.
The purpose of this study is to compare the effects of diluted hematocrit (HCT) levels of 35% versus 25% during hypothermic cardiopulmonary bypass (CPB) in infants with d-transposition of the great arteries, a malformation of the heart vessels.
Detailed description
BACKGROUND:
The optimal degree of hemodilution during profoundly hypothermic CPB remains controversial, and widely dissimilar hemodilution studies have evolved at centers that perform infant cardiac surgery. HCT, a measurement of the volume of red blood cells, is of interest in cardiopulmonary bypass. Higher HCT levels expose individuals to the risks of microvascular occlusion (blockage in the small blood vessels), while lower HCT levels may critically limit oxygen delivery to the brain and other organs. Preliminary research suggests that higher HCT levels provide superior brain and myocardial protection, but there have not been any studies that report on outcomes after usage of higher versus lower HCT levels.
DESIGN NARRATIVE:
In this single-center, prospective, randomized study, hemodilution to a HCT level of 35% versus 25% will be compared with respect to neurodevelopmental outcome and early postoperative course in infants with congenital heart disease. The first aim of this study will test the hypothesis that hemodilution to a HCT level of 35%, compared to a level of 25%, will be associated with superior central nervous system protection. The primary outcome variable will be developmental outcome at age 1 year, assessed using the Bayley Scales of Infant Development. Secondary outcome variables include the following: 1) tissue release of S-100 protein as a measure of cerebral cellular injury; 2) cerebral hemodynamics and oxygenation, determined by near infrared spectroscopy (NIRS); 3) intrinsic cerebral vasoregulation, measured by NIRS and transcranial Doppler; and 4) at age 1 year, neurologic examination, the MacArthur inventory, and structural and volumetric findings of magnetic resonance imaging (MRI).
The second aim of this study will test the hypothesis that hemodilution to a HCT level of 35%, compared to a level of 25%, will be associated with better early postoperative cardiovascular status. The primary outcome measure will be serum lactate levels 1 hour after the surgery. Secondary outcome measures will include the following: 1) the duration of postoperative endotracheal intubation, ICU stay, and hospital stay; 2) serum lactate levels; 3) the PaO2/FiO2 ratio; 4) levels of circulating pro-inflammatory cytokines; and 5) the percent change in total body water, estimated by bioelectrical impedance. The structure of the study will allow assessment of whether 1-year outcomes can be predicted by perioperative variables other than the HCT strategies. Through the use of novel techniques such as NIRS and volumetric MRI, the study may also provide insight into mechanisms by which HCT and other perioperative variables affect the brain. The information obtained from this study should be broadly generalized to infants with other forms of congenital heart disease undergoing early repair and should have substantial impact on clinical practice.
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
Key inclusion criteria (4 listed)
- Undergoing repair of ventricular septal defect within 9 months of study entry
- Tetralogy of fallot
- D-transposition of the great arteries
- Atrio-ventricular septal defect
Key exclusion criteria (5 listed)
- Birth weight less than 2.3 kg
- Recognizable phenotypic syndrome of congenital anomalies
- Extracardiac anomalies of greater than minor severity
- Previous cardiac surgery
- Associated cardiovascular anomalies requiring aortic arch reconstruction or additional open surgical procedures before the planned developmental follow-up
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 |
|---|---|---|
| Cardiopulmonary Bypass with Two Different Intra-Operative Hematocrits | Procedure or surgery | – |
| Thoracic Surgery | Procedure or surgery | – |
Primary outcome
Serum lactate levels (measured 1 hour after surgery)
Developmental outcome (measured by Bayley Scales of Infant Development at age 1 year)
8 secondary outcomes
Duration of postoperative endotracheal intubation, ICU stay, and hospital stay
PaO2/FiO2 ratio
Levels of circulating pro-inflammatory cytokines
Percent change in total body water, as estimated by bioelectrical impedance (measured 1 hour after surgery)
Tissue release of S-100 protein as a measure of cerebral cellular injury
Cerebral hemodynamics and oxygenation, as determined by near infrared spectroscopy (NIRS)
Intrinsic cerebral vasoregulation, as measured by NIRS and transcranial Doppler
Neurologic factors, as determined by neurologic examination, the MacArthur inventory, and structural and volumetric findings of MRI (measured at age 1 year)
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 14688685Jonas RA, Wypij D, Roth SJ, Bellinger DC, Visconti KJ, du Plessis AJ, Goodkin H, Laussen PC, Farrell DM, Bartlett J, McGrath E, Rappaport LJ, Bacha EA, Forbess JM, del Nido PJ, Mayer JE Jr, Newburger JW. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg. 2003 Dec;126(6):1765-74. doi: 10.1016/j.jtcvs.2003.04.003.
- Background: PubMed 15531739Bassan H, Gauvreau K, Newburger JW, Tsuji M, Limperopoulos C, Soul JS, Walter G, Laussen PC, Jonas RA, du Plessis AJ. Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery. Pediatr Res. 2005 Jan;57(1):35-41. doi: 10.1203/01.PDR.0000147576.84092.F9. Epub 2004 Nov 5.
- Background: PubMed 16243983Kussman BD, Wypij D, DiNardo JA, Newburger J, Jonas RA, Bartlett J, McGrath E, Laussen PC. An evaluation of bilateral monitoring of cerebral oxygen saturation during pediatric cardiac surgery. Anesth Analg. 2005 Nov;101(5):1294-1300. doi: 10.1213/01.ANE.0000180205.85490.85.
- Derived from this study: PubMed 27837950Rollins CK, Asaro LA, Akhondi-Asl A, Kussman BD, Rivkin MJ, Bellinger DC, Warfield SK, Wypij D, Newburger JW, Soul JS. White Matter Volume Predicts Language Development in Congenital Heart Disease. J Pediatr. 2017 Feb;181:42-48.e2. doi: 10.1016/j.jpeds.2016.09.070. Epub 2016 Nov 9.
- Derived from this study: PubMed 20606124Kussman BD, Wypij D, Laussen PC, Soul JS, Bellinger DC, DiNardo JA, Robertson R, Pigula FA, Jonas RA, Newburger JW. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010 Jul 20;122(3):245-54. doi: 10.1161/CIRCULATIONAHA.109.902338. Epub 2010 Jul 6.
- Derived from this study: PubMed 20453699Kipps AK, Wypij D, Thiagarajan RR, Bacha EA, Newburger JW. Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery. Pediatr Crit Care Med. 2011 Jan;12(1):52-6. doi: 10.1097/PCC.0b013e3181e30d43.
- Derived from this study: PubMed 19619781Soul JS, Robertson RL, Wypij D, Bellinger DC, Visconti KJ, du Plessis AJ, Kussman BD, Scoppettuolo LA, Pigula F, Jonas RA, Newburger JW. Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease. J Thorac Cardiovasc Surg. 2009 Aug;138(2):374-81. doi: 10.1016/j.jtcvs.2009.02.027. Epub 2009 Apr 10.
- Derived from this study: PubMed 18242267Newburger JW, Jonas RA, Soul J, Kussman BD, Bellinger DC, Laussen PC, Robertson R, Mayer JE Jr, del Nido PJ, Bacha EA, Forbess JM, Pigula F, Roth SJ, Visconti KJ, du Plessis AJ, Farrell DM, McGrath E, Rappaport LA, Wypij D. Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery. J Thorac Cardiovasc Surg. 2008 Feb;135(2):347-54, 354.e1-4. doi: 10.1016/j.jtcvs.2007.01.051.
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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 W. Newburger, MD, MPH study chair
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cardiopulmonary Bypass with Two Different Intra-Operative Hematocrits and Thoracic Surgery in people with Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
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 4 inclusion and 5 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: 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.
Where is the study taking place?
The record lists 1 site in United States. 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.
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.
What does the primary outcome measure?
Serum lactate levels (measured 1 hour after surgery). The study lists 2 primary outcomes in all. 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 NCT00006183, which also lists 8 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.