Intraventricular HemorrhagePhysDisNCT00665769
Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage
A study testing Hypercapnia and Normocapnia in people with Intraventricular Hemorrhage and Autoregulation, run by Baylor College of Medicine at 1 site in United States.
Trial summary
Annually, almost 5,000 extremely low birth weight (9 ounces to about 2 lbs) infants born in the US survive with severe bleeding in the brain (intraventricular hemorrhage); this devastating complication of prematurity is associated with many problems, including mental retardation, cerebral palsy, and learning… Read more about this study
- Who is it for?
- Ages 1 minute to 7 days
- Conditions the study is for
- Intraventricular Hemorrhage, Autoregulation
- What is being tested?
- Hypercapnia and Normocapnia
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Nov 2015
- Phase
- Interventional
- 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 1 minute to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ventilated ELBW (401-1000 grams) infants
- 23 to 30 weeks' gestation
- umbilical arterial catheter placed during newborn resuscitation
Who cannot join
- presence of complex congenital anomalies or chromosomal abnormality
- presence of central nervous system malformation
- infants with hydrops fetalis
- infants in extremis
- infants with early (<3 hour of age) intraventricular hemorrhage
Trial locations and contacts
1 site in 1 country.
About this study
Annually, almost 5,000 extremely low birth weight (9 ounces to about 2 lbs) infants born in the US survive with severe bleeding in the brain (intraventricular hemorrhage); this devastating complication of prematurity is associated with many problems, including mental retardation, cerebral palsy, and learning disabilities, that result in profound individual and familial consequences. In addition, lifetime care costs for these severely affected infants born in a single year exceed $3 billion. The huge individual and societal costs underscore the need for developing care strategies that may limit severe bleeding in the brain of these tiny infants. The overall goal of our research is to evaluate disturbances of brain blood flow in these tiny infants in order to predict which of them are at highest risk and to develop better intensive care techniques that will limit severe brain injury.
- Since most of these infants require ventilators (respirators) to survive, we will investigate how 2 different methods of ventilation affect brain injury. We believe that a new method of ventilation, allowing normal carbon dioxide levels, will normalize brain blood flow and lead to less bleeding in the brain.
- We will also examine how treatment for low blood pressure in these infants may be associated with brain injury. We believe that most very premature infants with low blood pressure actually do worse if they are treated. We think that by allowing the infants to normalize blood pressure on their own will allow them to stabilize blood flow to the brain leading to less intraventricular hemorrhage.
- In 10 premature infants with severe brain bleeding, we have developed a simple technique to identify intraventricular hemorrhage before it happens. Apparently, the heart rate of infants who eventually develop severe intraventricular hemorrhage is less variable than infants who do not develop this. We plan to test this method in a large group of infants, to be able to predict which infants are at highest risk of developing intraventricular hemorrhage and who could most benefit from interventions that would reduce disturbances of brain blood flow.
- Conditions
- Intraventricular Hemorrhage, Autoregulation
- Being tested
- Hypercapnia, Normocapnia
- Keywords
- hypercapnia, normocapnia, chronic lung disease, periventricular leukomalacia, intraventricular hemorrhage, hypotension, cerebral autoregulation, heart rate variability, autonomic nervous system, detrended fluctuation analysis
- Medical subject headings
- Hypercapnia, Leukomalacia, Periventricular, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HypercapniaOther
Also called hypercarbia, permissive hypercapnia
transcutaenous CO2 50-60 mm Hg
NormocapniaOther
Also called Normocarbia
transcutaneous CO2 35-45 mm Hg
| Study group | Role | What they receive |
|---|---|---|
| Hypercapnia | Placebo comparator | Hypercapnic ventilation. The goal will be to maintain transcutaneous CO2 55 mm Hg (50-60 mm Hg) during the first week of life, or until extubation. A written, laminated hypercapnic ventilator algorithm will be placed at the bedside. Receives: Other: Hypercapnia |
| Normocapnia | Active comparator | Normocapnic ventilation. The goal will be to maintain transcutaenous CO2 40 mm Hg (35-45 mm Hg) during the first week of life, or until extubation. A written, laminated normocapnic ventilator algorithm will be placed at the bedside. Receives: Other: Normocapnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of hypercapnia vs. normocapnia on the development of Grade II-IV intraventricular hemorrhage/periventricular leukomalacia (severe brain injury) and/or death
Measured: During first 2 weeks of life (intraventricular hemorrhage and/or death), initial hospitalization for periventricular leukomalacia
Secondary outcomes (3)
The effect of hypercapnia vs. normocapnia on the development of chronic lung disease (requirement of supplemental oxygen at 36 weeks corrected gestational age)
Measured: By 36 weeks corrected gestational age.
The effect of hypercapnia vs. normocapnia on abnormal results from MRIs
Measured: at term-equivalent age
The effect of hypercapnia vs. normocapnia on the development of pulmonary hemorrhage
Measured: During the initial hospitalization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2008 (estimated)
- Study startJun 2008
- Primary completionNov 2015
- Study completionNov 2015
Why it stopped: Recruitment was proceeding too slowly
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Intraventricular HemorrhageStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Christopher J. Rhee, MD, MS, Baylor University
- Investigators
- Jeffrey R. Kaiser, MD, MA, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00665769
- Sponsor's protocol ID
- H-31475
- Other IDs
- 1R01NS060674
- Acronym
- PhysDis
- Status last verified
- Mar 2022
- First submitted
- 22 Apr 2008
- Last updated
- 5 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hall RW, Kaiser JR. Hypotension and brain injury in premature infants. Pediatrics. 2008 Mar;121(3):654; author reply 654-5. doi: 10.1542/peds.2007-3602. No abstract available.
PubMed 18310222Kaiser JR, Gauss CH, Williams DK. Tracheal suctioning is associated with prolonged disturbances of cerebral hemodynamics in very low birth weight infants. J Perinatol. 2008 Jan;28(1):34-41. doi: 10.1038/sj.jp.7211848. Epub 2007 Oct 25.
PubMed 18165829Kaiser JR. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007 May;119(5):1039; author reply 1039-40. doi: 10.1542/peds.2007-0353. No abstract available.
PubMed 17473113Kaiser JR, Gauss CH, Pont MM, Williams DK. Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol. 2006 May;26(5):279-85. doi: 10.1038/sj.jp.7211492.
PubMed 16554847Kaiser JR, Gauss CH, Williams DK. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res. 2005 Nov;58(5):931-5. doi: 10.1203/01.pdr.0000182180.80645.0c.
PubMed 16257928Kaiser JR, Gauss CH, Williams DK. Surfactant administration acutely affects cerebral and systemic hemodynamics and gas exchange in very-low-birth-weight infants. J Pediatr. 2004 Jun;144(6):809-14. doi: 10.1016/j.jpeds.2004.03.022.
PubMed 15192631Tuzcu V, Nas S, Borklu T, Ugur A. Decrease in the heart rate complexity prior to the onset of atrial fibrillation. Europace. 2006 Jun;8(6):398-402. doi: 10.1093/europace/eul031. Epub 2006 May 10.
PubMed 16687424Rushing S, Ment LR. Preterm birth: a cost benefit analysis. Semin Perinatol. 2004 Dec;28(6):444-50. doi: 10.1053/j.semperi.2004.10.007.
PubMed 15693401van Bel F, de Winter PJ, Wijnands HB, van de Bor M, Egberts J. Cerebral and aortic blood flow velocity patterns in preterm infants receiving prophylactic surfactant treatment. Acta Paediatr. 1992 Jun-Jul;81(6-7):504-10. doi: 10.1111/j.1651-2227.1992.tb12283.x.
PubMed 1392362van de Bor M, Walther FJ. Cerebral blood flow velocity regulation in preterm infants. Biol Neonate. 1991;59(6):329-35. doi: 10.1159/000243368.
PubMed 1873365Lou HC, Lassen NA, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infant. J Pediatr. 1979 Jan;94(1):118-21. doi: 10.1016/s0022-3476(79)80373-x.
PubMed 758388Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007 Feb;119(2):299-305. doi: 10.1542/peds.2006-2434.
PubMed 17272619Fanaroff JM, Wilson-Costello DE, Newman NS, Montpetite MM, Fanaroff AA. Treated hypotension is associated with neonatal morbidity and hearing loss in extremely low birth weight infants. Pediatrics. 2006 Apr;117(4):1131-5. doi: 10.1542/peds.2005-1230.
PubMed 16585307van Ravenswaaij-Arts CM, Hopman JC, Kollee LA, van Amen JP, Stoelinga GB, van Geijn HP. The influence of respiratory distress syndrome on heart rate variability in very preterm infants. Early Hum Dev. 1991 Dec;27(3):207-21. doi: 10.1016/0378-3782(91)90195-9.
PubMed 1802672
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage
- ClinicalTrials.gov ID
- NCT00665769
- Acronym / sponsor ID
- PhysDis / H-31475
- Conditions
- Intraventricular Hemorrhage, Autoregulation
- Keywords
- hypercapnia, normocapnia, chronic lung disease, periventricular leukomalacia, intraventricular hemorrhage, hypotension, cerebral autoregulation, heart rate variability
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment was proceeding too slowly
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jun 2008
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 24 Apr 2008 (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.
Annually, almost 5,000 extremely low birth weight (9 ounces to about 2 lbs) infants born in the US survive with severe bleeding in the brain (intraventricular hemorrhage); this devastating complication of prematurity is associated with many problems, including mental retardation, cerebral palsy, and learning disabilities, that result in profound individual and familial consequences. In addition, lifetime care costs for these severely affected infants born in a single year exceed $3 billion. The huge individual and societal costs underscore the need for developing care strategies that may limit severe bleeding in the brain of these tiny infants. The overall goal of our research is to evaluate disturbances of brain blood flow in these tiny infants in order to predict which of them are at highest risk and to develop better intensive care techniques that will limit severe brain injury.
- Since most of these infants require ventilators (respirators) to survive, we will investigate how 2 different methods of ventilation affect brain injury. We believe that a new method of ventilation, allowing normal carbon dioxide levels, will normalize brain blood flow and lead to less bleeding in the brain.
- We will also examine how treatment for low blood pressure in these infants may be associated with brain injury. We believe that most very premature infants with low blood pressure actually do worse if they are treated. We think that by allowing the infants to normalize blood pressure on their own will allow them to stabilize blood flow to the brain leading to less intraventricular hemorrhage.
- In 10 premature infants with severe brain bleeding, we have developed a simple technique to identify intraventricular hemorrhage before it happens. Apparently, the heart rate of infants who eventually develop severe intraventricular hemorrhage is less variable than infants who do not develop this. We plan to test this method in a large group of infants, to be able to predict which infants are at highest risk of developing intraventricular hemorrhage and who could most benefit from interventions that would reduce disturbances of brain blood flow.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypercapnia | Placebo comparator | Other: HypercapniaHypercapnic ventilation. The goal will be to maintain transcutaneous CO2 55 mm Hg (50-60 mm Hg) during the first week of life, or until extubation. A written, laminated hypercapnic ventilator algorithm will be placed at the bedside. |
| Normocapnia | Active comparator | Other: NormocapniaNormocapnic ventilation. The goal will be to maintain transcutaenous CO2 40 mm Hg (35-45 mm Hg) during the first week of life, or until extubation. A written, laminated normocapnic ventilator algorithm will be placed at the bedside. |
Who may qualify
- Ages
- 1 minute to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- ventilated ELBW (401-1000 grams) infants
- 23 to 30 weeks' gestation
- umbilical arterial catheter placed during newborn resuscitation
Key exclusion criteria (5 listed)
- presence of complex congenital anomalies or chromosomal abnormality
- presence of central nervous system malformation
- infants with hydrops fetalis
- infants in extremis
- infants with early (<3 hour of age) intraventricular hemorrhage
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 |
|---|---|---|
| HypercapniaAlso: hypercarbia, permissive hypercapniatranscutaenous CO2 50-60 mm Hg | Other | Hypercapnia |
| NormocapniaAlso: Normocarbiatranscutaneous CO2 35-45 mm Hg | Other | Normocapnia |
Primary outcome
The effect of hypercapnia vs. normocapnia on the development of Grade II-IV intraventricular hemorrhage/periventricular leukomalacia (severe brain injury) and/or death
Time frame: During first 2 weeks of life (intraventricular hemorrhage and/or death), initial hospitalization for periventricular leukomalacia
3 secondary outcomes
The effect of hypercapnia vs. normocapnia on the development of chronic lung disease (requirement of supplemental oxygen at 36 weeks corrected gestational age)
Time frame: By 36 weeks corrected gestational age.
The effect of hypercapnia vs. normocapnia on abnormal results from MRIs
Time frame: at term-equivalent age
The effect of hypercapnia vs. normocapnia on the development of pulmonary hemorrhage
Time frame: During the initial hospitalization
Results and safety
The study was stopped early (reason given: Recruitment was proceeding too slowly). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
- Background: PubMed 18310222Hall RW, Kaiser JR. Hypotension and brain injury in premature infants. Pediatrics. 2008 Mar;121(3):654; author reply 654-5. doi: 10.1542/peds.2007-3602. No abstract available.
- Background: PubMed 18165829Kaiser JR, Gauss CH, Williams DK. Tracheal suctioning is associated with prolonged disturbances of cerebral hemodynamics in very low birth weight infants. J Perinatol. 2008 Jan;28(1):34-41. doi: 10.1038/sj.jp.7211848. Epub 2007 Oct 25.
- Background: PubMed 17473113Kaiser JR. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007 May;119(5):1039; author reply 1039-40. doi: 10.1542/peds.2007-0353. No abstract available.
- Background: PubMed 16554847Kaiser JR, Gauss CH, Pont MM, Williams DK. Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol. 2006 May;26(5):279-85. doi: 10.1038/sj.jp.7211492.
- Background: PubMed 16257928Kaiser JR, Gauss CH, Williams DK. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res. 2005 Nov;58(5):931-5. doi: 10.1203/01.pdr.0000182180.80645.0c.
- Background: PubMed 15192631Kaiser JR, Gauss CH, Williams DK. Surfactant administration acutely affects cerebral and systemic hemodynamics and gas exchange in very-low-birth-weight infants. J Pediatr. 2004 Jun;144(6):809-14. doi: 10.1016/j.jpeds.2004.03.022.
- Background: PubMed 16687424Tuzcu V, Nas S, Borklu T, Ugur A. Decrease in the heart rate complexity prior to the onset of atrial fibrillation. Europace. 2006 Jun;8(6):398-402. doi: 10.1093/europace/eul031. Epub 2006 May 10.
- Background: PubMed 15693401Rushing S, Ment LR. Preterm birth: a cost benefit analysis. Semin Perinatol. 2004 Dec;28(6):444-50. doi: 10.1053/j.semperi.2004.10.007.
- Background: PubMed 1392362van Bel F, de Winter PJ, Wijnands HB, van de Bor M, Egberts J. Cerebral and aortic blood flow velocity patterns in preterm infants receiving prophylactic surfactant treatment. Acta Paediatr. 1992 Jun-Jul;81(6-7):504-10. doi: 10.1111/j.1651-2227.1992.tb12283.x.
- Background: PubMed 1873365van de Bor M, Walther FJ. Cerebral blood flow velocity regulation in preterm infants. Biol Neonate. 1991;59(6):329-35. doi: 10.1159/000243368.
- Background: PubMed 758388Lou HC, Lassen NA, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infant. J Pediatr. 1979 Jan;94(1):118-21. doi: 10.1016/s0022-3476(79)80373-x.
- Background: PubMed 17272619Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007 Feb;119(2):299-305. doi: 10.1542/peds.2006-2434.
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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.
Jeffrey R. Kaiser, MD, MA principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypercapnia and Normocapnia in people with Intraventricular Hemorrhage and Autoregulation, run by Baylor College of Medicine 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 3 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: stopped early, as of the sponsor's last update on 5 Apr 2022. 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. Some participants in this study may receive a placebo. 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?
The study was stopped early (reason given: Recruitment was proceeding too slowly). Results are not available in the source record.
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?
The effect of hypercapnia vs. normocapnia on the development of Grade II-IV intraventricular hemorrhage/periventricular leukomalacia (severe brain injury) and/or death (time frame: During first 2 weeks of life (intraventricular hemorrhage and/or death), initial hospitalization for periventricular leukomalacia). 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 NCT00665769, which also lists 14 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 5 Apr 2022; AzTrials last refreshed its copy on 26 Oct 2026.