Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage (PhysDis)

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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. 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. 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. 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.

Condition or disease	Intervention/treatment	Phase
Intraventricular Hemorrhage; Autoregulation	Other: Hypercapnia; Other: Normocapnia	Not Applicable

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	103 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage
Study Start Date :	June 2008
Actual Primary Completion Date :	November 2015
Estimated Study Completion Date :	September 2017

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Placebo Comparator: Hypercapnia; 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; transcutaenous CO2 50-60 mm Hg; Other Names: hypercarbia; permissive hypercapnia
Active Comparator: Normocapnia; 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; transcutaneous CO2 35-45 mm Hg; Other Name: Normocarbia

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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. ]
2. The effect of hypercapnia vs. normocapnia on abnormal results from MRIs [ Time Frame: at term-equivalent age ]
3. The effect of hypercapnia vs. normocapnia on the development of pulmonary hemorrhage [ Time Frame: During the initial hospitalization ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	up to 7 Days (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Jeffrey R. Kaiser, MD, MA	Baylor College of Medicine

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

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.

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.

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.

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.

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.

Tuzcu V, Nas S, Börklü T, Ugur A. Decrease in the heart rate complexity prior to the onset of atrial fibrillation. Europace. 2006 Jun;8(6):398-402. Epub 2006 May 10.

Rushing S, Ment LR. Preterm birth: a cost benefit analysis. Semin Perinatol. 2004 Dec;28(6):444-50.

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.

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

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.

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.

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.

van Ravenswaaij-Arts CM, Hopman JC, Kollée 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.

Responsible Party:	Jeffrey Radin Kaiser, MD, MA, Professor of Pediatrics and Obstetrics and Gynecology, Baylor University
ClinicalTrials.gov Identifier:	NCT00665769 History of Changes
Other Study ID Numbers:	H-31475; 1R01NS060674 ( U.S. NIH Grant/Contract )
First Posted:	April 24, 2008
Last Update Posted:	February 7, 2017
Last Verified:	February 2017

Keywords provided by Jeffrey Radin Kaiser, MD, MA, Baylor University:

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

Additional relevant MeSH terms:

Hemorrhage; Cerebral Hemorrhage; Fetal Diseases; Infant, Newborn, Diseases; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders	Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pregnancy Complications