Approaches and Decisions for Acute Pediatric TBI Trial

Severe Traumatic Brain Injury Clinical Trial

— ADAPT  

Official title:

Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04077411
• Other study ID #: PRO13020047
• Secondary ID: U01NS081041
• Status: Completed
• 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
• 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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Severe Traumatic Brain Injury

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