Benchmark Evidence Led by Latin America: Trial of Intracranial Pressure - Pediatrics

Not Applicable

Recruiting

• Conditions: Severe Traumatic Brain Injury
• Interventions: Other: ICP; Other: CREVICE

• Registration Number: NCT05566431
• Lead Sponsor: University of Washington

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.

Study Timeline

• Study First Submitted: 2022-06-10
• Study First Submitted QC: 2022-10-01
• Study First Posted: 2022-10-04
• Study Start: 2023-03-22
• Status Verified: 2023-12
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-28
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 428

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ICP monitoring based Protocol	ICP	Arm one will use a consensus-developed management protocol for paediatric severe traumatic brain injury based on recommendations from the Brain Trauma Foundation Guidelines, which uses invasive intracranial pressure monitoring
No ICP Monitoring Protocol CREVICE	CREVICE	Arm two will use the Consensus-Revised Imaging and Clinical Examination (CREVICE) management protocol for paediatric severe traumatic brain injury based on imaging and clinical examination in the absence of invasive intracranial pressure monitoring

Primary Outcome Measures

Name	Time	Method
Pediatric Quality of Life Inventory (PedsQL)	6 months after injury	PedsQL is a generic, health-related quality of life instrument developed to measure the core dimensions of physical, cognitive, mental, social health, and role (school) function. Minimum and maximum values: 0-100. Higher scores have better outcomes.

Secondary Outcome Measures

Name	Time	Method
ICU length of stay	1 month average	ICU length of stay related to TBI management is through acute hospitalization and for an average of one (1) month.
Brain-specific interventions	1 month average	Total number of individual interventions directed at treating measured or suspected intracranial hypertension (i.e., brain-specific treatment) per hour summed over the duration of brain-specific treatment in ICU. Time Frame for brain-specific treatments is through acute hospitalization, an average of one (1) month and for GOS-E Peds is conducted 3 and 6 months after injury.
Glasgow Outcome Scale - Extended (GOS-E) Pediatric	3 and 6 months after injury	GOS-E is the most common measure of functional outcome in adult TBI trials. Its pediatric version is the primary outcome in the NINDS-funded ADAPT study. Minimum and maximum values: 1-8. Higher score has worse outcomes.
Mortality	3 and 6 months	Percent of participants who have died by the assessment time.
Pediatric Quality of Life Inventory (PedsQL)	3 months after injury	PedsQL is a generic, health-related quality of life instrument developed to measure the core dimensions of physical, cognitive, mental, social health, and role (school) function. Minimum and maximum values: 0 - 100. Higher the score means a better outcome.

Trial Locations

Locations (9)

Hospital Regional de Occidente San Juan de Dios; 🇬🇹 Quetzaltenango, Guatemala

Hospital Escuela; 🇭🇳 Tegucigalpa, Honduras

Hospital de Emergencias Pediátricas; 🇵🇪 Lima, Peru

Instituto Nacional de Salud del Niño - San Borja; 🇵🇪 Lima, Peru

University of Washington, Harborview Medical Center; 🇺🇸 Seattle, Washington, United States

Hospital Edgardo Rebagliati Martins; 🇵🇪 Lima, Peru

Hospital de Niños Benjamín Bloom; 🇸🇻 San Salvador, El Salvador

Hospital Regional de Esquintla; 🇬🇹 Escuintla, Guatemala

Hospital General San Juan de Dios; 🇬🇹 Guatemala City, Guatemala