Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
1000 participants
OBSERVATIONAL
2014-02-20
2018-08-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Children with severe TBI
Children with severe Traumatic Brain Injury
Observational
This is an observational study with no interventions.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Observational
This is an observational study with no interventions.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* ICP monitor placed as part of the child's standard care
* Glasgow Coma Scale (GCS) ≤ 8 after resuscitation
* Age 0 - 18 y
Exclusion Criteria
* 2\. Diagnosis of pregnancy in clinical subject
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
University of Pittsburgh
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Stephen Wisniewski
Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Michael J Bell, MD
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh Medical Center
Stephen R Wisniewski, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
University of California, San Diego / Rady's Children's Hospital
La Jolla, California, United States
Children's Hospital of Los Angeles
Los Angeles, California, United States
UCLA Mattel Children's Hospital
Los Angeles, California, United States
UC Davis Medical Center
West Sacramento, California, United States
Children's Hospital Colorado
Denver, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Miami Children's Hospital
Miami, Florida, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
University of Iowa Children's Hospita
Iowa City, Iowa, United States
John Hopkins Children's Center of Baltimore
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Boston Children's Hospital / Harvard University
Boston, Massachusetts, United States
Wayne State University in Detroit / Children's Hospital of Michigan
Detroit, Michigan, United States
Washington University - St. Louis
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Carolinas Medical Center Levine Children's Hospital
Charlotte, North Carolina, United States
University of Cincinnati / Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Penn State University - Hershey
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
University of Tennessee / Le Bonheur Children's Hospita
Memphis, Tennessee, United States
UT Southwestern / Children's Medical Center at Dallas
Dallas, Texas, United States
Texas Children's Hospital (Baylor College of Medicine)
Houston, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, United States
University of Washington - Seattle
Seattle, Washington, United States
University of Wisconsin - Madison
Madison, Wisconsin, United States
Children's Health Queensland Hospital and Health Service
Brisbane, , Australia
Royal Children's Hospital
Melbourne, , Australia
Princess Margaret Hospital
Perth, , Australia
All India Institute of Medical Sciences
New Delhi, , India
Erasmus Medical Center Children's Hospital
Rotterdam, , Netherlands
Starship Children's Hospital
Auckland, , New Zealand
University of Cape Town
Cape Town, , South Africa
Hospital Vall d'Hebron
Barcelona, , Spain
Birmingham Children's Hospita
Birmingham, , United Kingdom
University Hospitals Bristol
Bristol, , United Kingdom
Addenbrookes Hospital
Cambridge, , United Kingdom
Leeds Teaching Hospital
Leeds, , United Kingdom
Alder Hey Children's
Liverpool, , United Kingdom
King's College Hospital
London, , United Kingdom
Great Ormond Street
London, , United Kingdom
Newcastle upon Tyne Hospital
Newcastle upon Tyne, , United Kingdom
University Hospital Southampton
Southampton, , United Kingdom
Royal Manchester Children's Hospital
Victoria, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Sarnaik A, Ferguson NM, O'Meara AMI, Agrawal S, Deep A, Buttram S, Bell MJ, Wisniewski SR, Luther JF, Hartman AL, Vavilala MS; Investigators of the ADAPT Trial. Age and Mortality in Pediatric Severe Traumatic Brain Injury: Results from an International Study. Neurocrit Care. 2018 Jun;28(3):302-313. doi: 10.1007/s12028-017-0480-x.
Bell MJ, Adelson PD, Wisniewski SR; Investigators of the ADAPT Study,. Challenges and opportunities for pediatric severe TBI-review of the evidence and exploring a way forward. Childs Nerv Syst. 2017 Oct;33(10):1663-1667. doi: 10.1007/s00381-017-3530-y. Epub 2017 Sep 6.
Miller Ferguson N, Sarnaik A, Miles D, Shafi N, Peters MJ, Truemper E, Vavilala MS, Bell MJ, Wisniewski SR, Luther JF, Hartman AL, Kochanek PM; Investigators of the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury (ADAPT) Trial. Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury. Crit Care Med. 2017 Aug;45(8):1398-1407. doi: 10.1097/CCM.0000000000002378.
Larsen GY, Schober M, Fabio A, Wisniewski SR, Grant MJ, Shafi N, Bennett TD, Hirtz D, Bell MJ. Structure, Process, and Culture Differences of Pediatric Trauma Centers Participating in an International Comparative Effectiveness Study of Children with Severe Traumatic Brain Injury. Neurocrit Care. 2016 Jun;24(3):353-60. doi: 10.1007/s12028-015-0218-6.
Ahmed N, Russo L, Kuo YH. Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" (ADAPT) Dataset, 2014-2017. Pediatr Crit Care Med. 2024 Aug 1;25(8):710-719. doi: 10.1097/PCC.0000000000003526. Epub 2024 May 8.
Surtees TL, Kumar I, Garton HJL, Rivas-Rodriguez F, Parmar H, McCaffery H, Riebe-Rodgers J, Shellhaas RA. Levetiracetam Prophylaxis for Children Admitted With Traumatic Brain Injury. Pediatr Neurol. 2022 Jan;126:114-119. doi: 10.1016/j.pediatrneurol.2021.10.009. Epub 2021 Oct 19.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PRO13020047
Identifier Type: -
Identifier Source: org_study_id