Approaches and Decisions for Acute Pediatric TBI Trial (ADAPT)

Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial

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.

Study Overview

• Status: Completed
• Conditions: Severe Traumatic Brain Injury
• Intervention / Treatment: Other: Observational

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.

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Children's Health Queensland Hospital and Health Service
  • Melbourne, Australia
    • Royal Children's Hospital
  • Perth, Australia, 6008
    • Princess Margaret Hospital
• India
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
• Netherlands
  • Rotterdam, Netherlands, 3015 GJ
    • Erasmus Medical Center Children's Hospital
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Hospital
• South Africa
  • Cape Town, South Africa
    • University of Cape Town
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
• United Kingdom
  • Birmingham, United Kingdom, 6NH
    • Birmingham Children's Hospita
  • Bristol, United Kingdom
    • University Hospitals Bristol
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital
  • Leeds, United Kingdom, LS 7TF
    • Leeds Teaching Hospital
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's
  • London, United Kingdom, SE5 9NY
    • King's College Hospital
  • London, United Kingdom, WC1N 1EH
    • Great Ormond Street
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Newcastle upon Tyne Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton
  • Victoria, United Kingdom, 3052
    • Royal Manchester Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego / Rady's Children's Hospital
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Los Angeles, California, United States, 90095
      • UCLA Mattel Children's Hospital
    • West Sacramento, California, United States, 95798
      • UC Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Iowa
    • Iowa City, Iowa, United States, 52252
      • University of Iowa Children's Hospita
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Children's Center of Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02241
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 414413
      • Boston Children's Hospital / Harvard University
  • Michigan
    • Detroit, Michigan, United States, 13201
      • Wayne State University in Detroit / Children's Hospital of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63112
      • Washington University - St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28260
      • Carolinas Medical Center Levine Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati / Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43271
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University - Hershey
    • Philadelphia, Pennsylvania, United States, 19178
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh of UPMC
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee / Le Bonheur Children's Hospita
  • Texas
    • Dallas, Texas, United States, 75284
      • UT Southwestern / Children's Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital (Baylor College of Medicine)
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU
  • Washington
    • Seattle, Washington, United States, 98185
      • University of Washington - Seattle
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with severe traumatic brain injury (TBI)

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 1. ICP Monitor placed at another hospital
• 2. Diagnosis of pregnancy in clinical subject

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with severe TBI; Children with severe Traumatic Brain Injury	Other: Observational; This is an observational study with no interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Outcome Score - Extended Pediatrics	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)	6 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Michael J Bell, MD, University of Pittsburgh Medical Center; Principal Investigator: Stephen R Wisniewski, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2014
• Primary Completion (Actual): September 26, 2016
• Study Completion (Actual): August 28, 2018

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: TBI; Neuropsychology; Cerebrospinal fluid; Metabolism; Intracranial hypertension; Severe Traumatic Brain Injury; Hypersmolar therapies; Prophylactic hyperventilation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: PRO13020047; U01NS081041 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study data will be released to the general public through FITBIR. ADAPT will adhere to all FITBIR policies and procedures.
• IPD Sharing Time Frame: One year after publication of main results paper.

IPD Sharing Access Criteria

Investigators requesting and receiving FITBIR data are expected to:

• Submit a Data Access Request;
• Protect data confidentiality;
• Ensure that data security measures are in place;
• Notify the Data Access and Quality Committee of policy violations;
• Submit annual progress reports detailing significant research findings; and
• Include acknowledgements of the FITBIR Informatics System in all publications and presentations.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No