Clinical trial NCT05566431: Benchmark Evidence Led by Latin America: Trial of Intracranial Pressure - Pediatrics
Official title: Pediatric Severe Traumatic Brain Injury in Latin America - A Randomized Trial Comparing Two Management Protocols
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Severe Traumatic Brain Injury
Keywords: sTBI
ICP monitoring
randomized controlled trial
TBI management
Latin America
pediatric
Phase III
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-10-04
Enrollment: 428
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In a Phase III multicenter, parallel-group, randomized superiority trial in 428 children with sTBI from 7 Latin American pediatric trauma centers, the objective is to test the efficacy of the treatment protocol from the Guidelines based on ICP monitoring among children with sTBI in improving global outcome measured by Pediatric Quality of Life Inventory (PedsQL) 6 mos after injury compared to treatment based on a non-invasive imaging \& clinical examination (CREVICE) protocol specifically modified for a pediatric population.
Primary purpose: TREATMENT

Brief summary: Narrative:

Worldwide, traumatic brain injury (TBI) is a leading cause of death and disability among children and adolescents. The Investigators aim to test whether pediatric TBI treatment guided by invasive intracranial pressure monitoring produces better patient outcomes than care guided by a protocol without invasive monitoring. Study findings will inform clinical practice in treating pediatric severe TBI globally. Focused didactic and experience-based learning opportunities will increase the research capacity of pediatric intensivists in Latin America.

Detailed description: Abstract:

Children who survive severe traumatic brain injury (sTBI) live with profound impairments that alter their development and future possibilities. Worldwide, TBI is the leading cause of death and disability for children/ adolescents with the US annual incidence 6 times greater than MS, HIV/AIDS, spinal cord injury, and breast cancer combined.

Our primary focus for scientific investigation is to conduct a high quality randomized controlled trial addressing a critical TBI management question: Does using a protocol with information from intracranial pressure (ICP) monitoring to direct treatment of children with sTBI improve outcomes vs an aggressive management protocol based on imaging and clinical examination alone? This follows on our adult ICP study which found no outcome differences and has occasioned re-thinking of treatment guidelines for sTBI patients \>13. A separate study is essential because children are not simply small adults and some treatment approaches carry age-related additional risks. Thus, study findings will inform US and global clinical practice.

This trial will be conducted in 8 Latin American pediatric ICUs where infrastructures and practice patterns are optimal for strong internal validity and resources represent trauma care in the developing world. The successful adolescent/adult BEST TRIP trial, which collected high-quality data in similar environments (cited \> 900 times) underscores the feasibility of this approach.

Specific Aim: In a Phase III randomized superiority trial in 428 children with sTBI from 8 Latin American pediatric trauma centers, test the effect on outcomes of management of sTBI guided by a protocol using information from ICP monitors vs. management using a protocol that uses imaging and clinical exams to guide treatment.

Hypothesis #1: Children with severe TBI whose acute care treatment is managed using a protocol based on data from ICP monitoring will have significantly lower mortality and better quality of life and global outcome at 6 months post-trauma than those whose treatment is managed with a protocol based on imaging and clinical exam. The primary measure of functional recovery is the PedsQL at 6 months. A secondary measure is GOSE-Peds.

Hypothesis #2: Incorporating ICP monitoring into sTBI patient care will minimize secondary complications, decrease length of stay in ICU and decrease brain-specific treatments.

Specific Aim: The Investigators will train personnel in centers new to research how to conduct high-quality scientific studies, and will extend the training for the personnel with whom the Investigators have been working, solidifying previous capacity-building efforts, and initiating new efforts.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form by the parent(s) or guardian(s)
2. Non-penetrating TBI
3. Admission to study hospital within 24 hours of injury
4. Total GCS score ≤ 8 on admission or within first 48 hours after injury (measured using pediatric GCS 1 for children \< 2 years old and standard GCS for older children)
5. Age 1 through 12 years
6. Able to randomize:

   * Within 24 hours of injury (for patients with GCS ≤ 8 on admission) OR
   * Within 24 hours of deterioration (for patients deteriorating to GCS ≤ 8 within 48 hours of injury)

Exclusion Criteria:

1. Motor GCS score of 6
2. GCS of 3 with bilaterally fixed and dilated pupils
3. Injury thought to be intentionally inflicted by a family member or caregiver.

Primary outcomes:
measure: Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 6 months after injury
Secondary outcomes:
measure: Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 3 months after injury
measure: Glasgow Outcome Scale - Extended (GOS-E) Pediatric
timeFrame: 3 and 6 months after injury
measure: Mortality
timeFrame: 3 and 6 months
measure: Brain-specific interventions
timeFrame: 1 month average
measure: ICU length of stay
timeFrame: 1 month average
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington, Harborview Medical Center
state: Washington
city: San Salvador
country: El Salvador
facility: Hospital de Niños Benjamín Bloom
city: Escuintla
country: Guatemala
facility: Hospital Regional de Esquintla
city: Guatemala City
country: Guatemala
facility: Hospital General San Juan de Dios
city: Quetzaltenango
country: Guatemala
facility: Hospital Regional de Occidente San Juan de Dios
city: Tegucigalpa
country: Honduras
facility: Hospital Escuela
city: Lima
country: Peru
facility: Hospital de Emergencias Pediátricas
city: Lima
country: Peru
facility: Hospital Edgardo Rebagliati Martins
city: Lima
country: Peru
facility: Instituto Nacional de Salud del Niño - San Borja
Study officials:
affiliation: University of Washington
name: Randall Chesnut, MD
role: PRINCIPAL_INVESTIGATOR
References: