Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage

This study is currently recruiting participants.
Verified January 2012 by University of Arkansas
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00665769
First received: April 22, 2008
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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 Intervention
Intraventricular Hemorrhage
Autoregulation
Device: Hypercapnia
Other: Normocapnia

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • The effect of hypercapnia vs. normocapnia on the development of intraventricular hemorrhage during the first week of life [ Time Frame: During first week of life ] [ Designated as safety issue: Yes ]
  • The effect of hypercapnia and hypotension on the capacity for cerebral autoregulation [ Time Frame: First week of life ] [ Designated as safety issue: No ]
  • The development of intraventricular hemorrhage based upon abnormal heart rate variability [ Time Frame: first week of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The effect of hypercapnia vs. normocapnia on the development of chronic lung disease during premature infants' initial hospitalization [ Time Frame: By 36 weeks corrected gestational age. ] [ Designated as safety issue: Yes ]
  • The effect of hypercapnia vs. normocapnia on the development of respiratory complications (number of days on mechanical ventilation, air leaks, number of reintubations) [ Time Frame: During the initial newborn hospitalization ] [ Designated as safety issue: Yes ]
  • The effect of hypercapnia vs. normocapnia survival and length of hospital stay. [ Time Frame: During the initial newborn hospitalization ] [ Designated as safety issue: Yes ]
  • The effect of hypercapnia vs. normocapnia on the development of periventricular leukomalacia [ Time Frame: During the initial hospitalizaiton ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: June 2008
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Hypercapnic ventilation. The goal will be to maintain tcPCO2 55 mm Hg (50-60 mm Hg) and pH ≥7.20 (based on intermittent arterial blood gas determinations) during the first week of life, or until extubation. A written, laminated hypercapnic ventilator algorithm will be placed at the bedside.
Device: Hypercapnia
tcPCO2 50-60 mm Hg
Other Names:
  • hyercarbia
  • permissive hypercapnia
Placebo Comparator: B
Normocapnic ventilation. The goal will be to maintain tcPCO2 40 mm Hg (35-45 mm Hg) and pH ≥7.25 (based on intermittent arterial blood gas determinations) during the first week of life, or until extubation. A written, laminated normocapnic ventilator algorithm will be placed at the bedside.
Other: Normocapnia
tcPCO2 35-45 mm Hg
Other Name: Normocarbia

  Eligibility

Ages Eligible for Study:   up to 7 Days
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665769

Contacts
Contact: Jeffrey R. Kaiser, MD, MA 501-364-1056 kaiserjeffreyr@uams.edu
Contact: Natalie C. Sikes, RN 501-686-7580 sikesnataliec@uams.edu

Locations
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Jeffrey R. Kaiser, MD, MA     501-364-1056     kaiserjeffreyr@uams.edu    
Contact: Natalie C. Sikes, RN     501-686-7580     sikesnataliec@uams.edu    
Principal Investigator: Jeffrey R. Kaiser, MD, MA            
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Jeffrey R. Kaiser, MD, MA University of Arkansas
  More Information

Publications:

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00665769     History of Changes
Other Study ID Numbers: 102864, 1RO1NS60674-01A1
Study First Received: April 22, 2008
Last Updated: January 18, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Arkansas:
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:
Fetal Diseases
Infant, Newborn, Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Pregnancy Complications

ClinicalTrials.gov processed this record on May 21, 2013