Approaches and Decisions for Acute Pediatric TBI Trial
- Conditions
- Severe Traumatic Brain Injury
- Interventions
- Other: Observational
- Registration Number
- NCT04077411
- Lead Sponsor
- University of Pittsburgh
- Brief Summary
Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT) is an international research study designed to evaluate the impact of interventions on the outcomes of children with severe traumatic brain injury.
Pediatric traumatic brain injury (TBI) is the leading killer of children, resulting in more than 7000 deaths and $2 billion in acute care costs each year. Despite this large burden of disease, advances in the field have been limited due to weak evidenced-based guidelines and the limitations of randomized, controlled trials (RCTs) to demonstrate efficacy of single treatment strategies due to wide treatment variability. ADAPT is a practical study design in a novel approach - an observational cohort study designed to evaluate the association of 6 aspects of pediatric TBI care with outcomes using statistical modeling to correct for confounding variables. Completion of this study will provide compelling evidence to change clinical practices, provide evidence for new Level II recommendations for future guidelines and lead to improved research protocols that would limit variability in TBI treatments - helping children immediately through better clinical practices and ultimately through more effective investigation.
- Detailed Description
Traumatic brain injury (TBI) is the leading cause of death in children in the US. According to the CDC, 7440 children died of TBI in 2005, but this likely underestimates the full burden of the disease. Based on the current best estimates for severe pediatric TBI (20% mortality, 50.6% unfavorable 6 mo outcome, mean age 9 y), each year 37,200 children suffer a severe TBI with up to 1.3 million life-years potentially adversely affected.
Incremental improvement in outcomes could make enormous differences for the health of children, but such advances have remained elusive. Dozens of injury mechanisms have been identified after experimental TBI, yet no mitigating treatments have been translated into clinical practice. Randomized controlled trials (RCTs) of therapies, from steroids to novel pharmaceutical agents to hypothermia, have failed for adult and pediatric TBI victims. Single-center experiences have contributed to understanding, yet these largely remain insufficiently powerful to change practice. Recently, evidenced-based guidelines for 15 aspects of pediatric TBI were published that provide no level I and only 4 Level II recommendations - with such recommendations indicating therapies that "must be done" or "should be considered" based on the literature, respectively. Disappointingly, 3 of these recommendations advised against specific interventions (hypothermia, steroids and immune-enhanced diets) - emphasizing the uncertainty of the effectiveness of many commonly used therapies that leads to wide variations in clinical practice. Unsurprisingly, significant variations of clinical outcomes and basic treatment strategies for TBI have been observed. The IMPACT study merged data from over 9000 adults with TBI from 11 trials and demonstrated significant variations in outcomes from clinical sites. Similar variations in outcomes in children with TBI can be found using various administrative databases, with mortality rates varying between 12.2% - 34.4% in 11 US states. There are also variations in strategies within an international consortium and a recently completed RCT - with marked variations in strategies for first-line intracranial hypertension treatments, prevention of common secondary insults and metabolic support after pediatric TBI.
The paucity of data to create robust guidelines, the failure of RCTs that tested a wide-variety of putative mechanisms and variations in outcomes and in clinical practices argues that the current understanding of contemporary therapies is inadequate. Because neither retrospective analyses from available databases nor self-reported variations in practices can determine optimal therapeutic strategies for these contemporaneous strategies, a new approach is urgently needed.
ADAPT is a large, prospective, observational cohort study using an international consortium including sites from the US, EU and UK. Children with severe TBI \[Glasgow coma scale (GCS) score ≤ 8 with intracranial pressure (ICP) monitoring, n = 1000, \>32 sites\] will be studied. The local standard of care at each site will be used and extensive data collection over the first 7 days after TBI will be performed to interrogate the effectiveness of strategies for intracranial hypertension, mitigation of specific secondary insults and metabolism.
Several statistical approaches, often used in comparative effectiveness research (CER) to control for measured confounding effects, will test the following aims:
Specific Aim 1: Compare the effectiveness of first-line intracranial hypertension strategies on outcome. Intracranial hypertension management is a mainstay of TBI care yet evidence for utilization the first-line therapies of cerebrospinal fluid (CSF) diversion and use of hyperosmolar solutions, is incomplete.
Aim 1a: Determine the effect of CSF diversion strategies (continuous drainage, intermittent drainage and none) on outcome. Aim 1b: Determine the effect of hyperosmolar therapies (hypertonic saline, mannitol) on outcome.
Specific Aim 2: Compare the effectiveness of strategies that mitigate specific secondary insults on outcome. Prophylactic hyperventilation (HV) and hypoxia may worsen outcome after TBI but have been inadequately studied.
Aim 2a: Determine the effect of prophylactic HV (CO2 \< 30 mm Hg) on outcome.
Aim 2b: Determine the effect of hypoxia detection with brain tissue oxygen monitoring (PbO2) on outcome.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1000
- Admission to a study site for treatment of severe traumatic brain injury
- ICP monitor placed as part of the child's standard care
- Glasgow Coma Scale (GCS) ≤ 8 after resuscitation
- Age 0 - 18 y
-
- ICP Monitor placed at another hospital
-
- Diagnosis of pregnancy in clinical subject
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Children with severe TBI Observational Children with severe Traumatic Brain Injury
- Primary Outcome Measures
Name Time Method Glasgow Outcome Score - Extended Pediatrics 6 months Physician-rated assessment of functional outcome. Problems in functioning should have deteriorated from premorbid level. The categories are:
8 - Death 7 - Vegetative State (VS) 6 - Lower Severe Disability (Lower SD) 5 - Upper Severe Disability (Upper SD) 4 - Lower Moderate Disability (Lower MD) 3 - Upper Moderate Disability (Upper MD) 2 - Lower Good Recovery (Lower GR)
1 - Upper Good Recovery (Upper GR)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (48)
Penn State University - Hershey
🇺🇸Hershey, Pennsylvania, United States
UC Davis Medical Center
🇺🇸West Sacramento, California, United States
Erasmus Medical Center Children's Hospital
🇳🇱Rotterdam, Netherlands
Leeds Teaching Hospital
🇬🇧Leeds, United Kingdom
University of Cape Town
🇿🇦Cape Town, South Africa
Princess Margaret Hospital
🇦🇺Perth, Australia
University Hospitals Bristol
🇬🇧Bristol, United Kingdom
Alder Hey Children's
🇬🇧Liverpool, United Kingdom
University of Iowa Children's Hospita
🇺🇸Iowa City, Iowa, United States
Washington University - St. Louis
🇺🇸Saint Louis, Missouri, United States
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Carolinas Medical Center Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Royal Children's Hospital
🇦🇺Melbourne, Australia
Royal Manchester Children's Hospital
🇬🇧Victoria, United Kingdom
Children's Health Queensland Hospital and Health Service
🇦🇺Brisbane, Australia
University of Wisconsin - Madison
🇺🇸Madison, Wisconsin, United States
King's College Hospital
🇬🇧London, United Kingdom
Starship Children's Hospital
🇳🇿Auckland, New Zealand
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UCLA Mattel Children's Hospital
🇺🇸Los Angeles, California, United States
John Hopkins Children's Center of Baltimore
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
UT Southwestern / Children's Medical Center at Dallas
🇺🇸Dallas, Texas, United States
University of California, San Diego / Rady's Children's Hospital
🇺🇸La Jolla, California, United States
Boston Children's Hospital / Harvard University
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Tennessee / Le Bonheur Children's Hospita
🇺🇸Memphis, Tennessee, United States
University of Washington - Seattle
🇺🇸Seattle, Washington, United States
Birmingham Children's Hospita
🇬🇧Birmingham, United Kingdom
Miami Children's Hospital
🇺🇸Miami, Florida, United States
University of Cincinnati / Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Texas Children's Hospital (Baylor College of Medicine)
🇺🇸Houston, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Wayne State University in Detroit / Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Great Ormond Street
🇬🇧London, United Kingdom
Newcastle upon Tyne Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
University Hospital Southampton
🇬🇧Southampton, United Kingdom
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
Children's Hospital Colorado
🇺🇸Denver, Colorado, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Richmond at VCU
🇺🇸Richmond, Virginia, United States