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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04077411
Other study ID # PRO13020047
Secondary ID U01NS081041
Status Completed
Phase
First received
Last updated
Start date February 20, 2014
Est. completion date August 28, 2018

Study information

Verified date March 2023
Source University of Pittsburgh
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 1000
Est. completion date August 28, 2018
Est. primary completion date September 26, 2016
Accepts healthy volunteers No
Gender All
Age group N/A to 18 Years
Eligibility 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 Design


Intervention

Other:
Observational
This is an observational study with no interventions.

Locations

Country Name City State
Australia Children's Health Queensland Hospital and Health Service Brisbane
Australia Royal Children's Hospital Melbourne
Australia Princess Margaret Hospital Perth
India All India Institute of Medical Sciences New Delhi
Netherlands Erasmus Medical Center Children's Hospital Rotterdam
New Zealand Starship Children's Hospital Auckland
South Africa University of Cape Town Cape Town
Spain Hospital Vall d'Hebron Barcelona
United Kingdom 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 Great Ormond Street London
United Kingdom King's College Hospital 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 States Children's Healthcare of Atlanta Atlanta Georgia
United States John Hopkins Children's Center of Baltimore Baltimore Maryland
United States Children's Hospital of Alabama Birmingham Alabama
United States Boston Children's Hospital / Harvard University Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
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 UT Southwestern / Children's Medical Center at Dallas Dallas Texas
United States Children's Hospital Colorado Denver Colorado
United States Wayne State University in Detroit / Children's Hospital of Michigan Detroit Michigan
United States Penn State University - Hershey Hershey Pennsylvania
United States Texas Children's Hospital (Baylor College of Medicine) Houston Texas
United States University of Iowa Children's Hospita Iowa City Iowa
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 University of Wisconsin - Madison Madison Wisconsin
United States University of Tennessee / Le Bonheur Children's Hospita Memphis Tennessee
United States Miami Children's Hospital Miami Florida
United States University of Nebraska Medical Center Omaha Nebraska
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Children's Hospital of Richmond at VCU Richmond Virginia
United States Washington University - St. Louis Saint Louis Missouri
United States Primary Children's Hospital Salt Lake City Utah
United States University of Washington - Seattle Seattle Washington
United States Children's National Medical Center Washington District of Columbia
United States UC Davis Medical Center West Sacramento California

Sponsors (2)

Lead Sponsor Collaborator
University of Pittsburgh National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Australia,  India,  Netherlands,  New Zealand,  South Africa,  Spain,  United Kingdom, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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
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