Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage

NCT00665769 | Terminated DMC

• 2 other identifiers: H-314751R01NS060674
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief 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 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.

1. 1.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.
2. 2.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.
3. 3.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

Keywords

hypercapnia; normocapnia; chronic lung disease; periventricular leukomalacia; intraventricular hemorrhage; hypotension; cerebral autoregulation; heart rate variability; autonomic nervous system; detrended fluctuation analysis

Outcome Measures

Primary Outcomes (1)

• The effect of hypercapnia vs. normocapnia on the development of Grade II-IV intraventricular hemorrhage/periventricular leukomalacia (severe brain injury) and/or death

  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)

  By 36 weeks corrected gestational age.

• The effect of hypercapnia vs. normocapnia on abnormal results from MRIs

  at term-equivalent age

• The effect of hypercapnia vs. normocapnia on the development of pulmonary hemorrhage

  During the initial hospitalization

Study Arms (2)

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.

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.

Other: Normocapnia

Interventions

Hypercapnia OTHER

transcutaenous CO2 50-60 mm Hg

Also known as: hypercarbia, permissive hypercapnia

Hypercapnia

Normocapnia OTHER

transcutaneous CO2 35-45 mm Hg

Also known as: Normocarbia

Normocapnia

Eligibility Criteria

• Age: 1 Minute - 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ventilated ELBW (401-1000 grams) infants
• to 30 weeks' gestation
• umbilical arterial catheter placed during newborn resuscitation

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (14)

• 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.

  PMID: 18310222 BACKGROUND

• Kaiser 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.

  PMID: 18165829 BACKGROUND

• Kaiser 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.

  PMID: 17473113 BACKGROUND

• Kaiser 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.

  PMID: 16554847 BACKGROUND

• Kaiser 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.

  PMID: 16257928 BACKGROUND

• Kaiser 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.

  PMID: 15192631 BACKGROUND

• Tuzcu 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.

  PMID: 16687424 BACKGROUND

• Rushing 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.

  PMID: 15693401 BACKGROUND

• van 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.

  PMID: 1392362 BACKGROUND

• van de Bor M, Walther FJ. Cerebral blood flow velocity regulation in preterm infants. Biol Neonate. 1991;59(6):329-35. doi: 10.1159/000243368.

  PMID: 1873365 BACKGROUND

• Lou 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.

  PMID: 758388 BACKGROUND

• Fabres 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.

  PMID: 17272619 BACKGROUND

• Fanaroff 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.

  PMID: 16585307 BACKGROUND

• van 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.

  PMID: 1802672 BACKGROUND

MeSH Terms

Conditions

Hypercapnia; Leukomalacia, Periventricular; Hypotension

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalomalacia; Vascular Diseases; Cardiovascular Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jeffrey R. Kaiser, MD, MA

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Obstetrics and Gynecology

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 24, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 5, 2022

Record last verified: 2022-03

Locations

US (1)