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

Sponsor

University of Washington (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05566431

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

428

Enrollment

Locations

Arms

45.7

Anticipated Duration (Months)

47.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Traumatic Brain Injury	Other: ICP Other: CREVICE	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

428 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Single (Outcomes Assessor)

Masking Description:

Outcome assessors will not go into the ICU when a study participant is being treated, unmasked study staff will not inform the outcome assessor which protocol was used for a participant. and outcome assessors will remind participant's parents to refrain for telling them which treatment protocol was used for the participant.

Primary Purpose:

Treatment

Official Title:

Pediatric Severe Traumatic Brain Injury in Latin America - A Randomized Trial Comparing Two Management Protocols

Anticipated Study Start Date :

Oct 10, 2022

Anticipated Primary Completion Date :

Jul 31, 2026

Anticipated Study Completion Date :

Jul 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ICP monitoring based Protocol 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	Other: ICP The intervention is a management protocol that includes ICP monitoring for children with severe traumatic brain injury Other Names: Intracranial-pressure-monitoring-based management protocol
Active Comparator: No ICP Monitoring Protocol 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	Other: CREVICE The intervention is a management protocol that is based on imaging and clinical examinations without ICP monitoring for children with severe traumatic brain injury Other Names: Imaging-and-clinical-examination-based management protocol

Arm

Intervention/Treatment

Active Comparator: ICP monitoring based Protocol

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

Other: ICP

The intervention is a management protocol that includes ICP monitoring for children with severe traumatic brain injury

Other Names:

Intracranial-pressure-monitoring-based management protocol

Active Comparator: No ICP Monitoring Protocol 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

Other: CREVICE

The intervention is a management protocol that is based on imaging and clinical examinations without ICP monitoring for children with severe traumatic brain injury

Other Names:

Imaging-and-clinical-examination-based management protocol

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form by the parent(s) or guardian(s)
Non-penetrating TBI
Admission to study hospital within 24 hours of injury
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)
Age 1 through 12 years
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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Washington, Harborview Medical Center	Seattle	Washington	United States	98104
2	Hospital de Niños Benjamín Bloom	San Salvador		El Salvador
3	Hospital Regional de Esquintla	Escuintla		Guatemala
4	Hospital General San Juan de Dios	Guatemala City		Guatemala
5	Hospital Regional de Occidente San Juan de Dios	Quetzaltenango		Guatemala
6	Hospital Escuela	Tegucigalpa		Honduras
7	Hospital de Emergencias Pediátricas	Lima		Peru
8	Hospital Edgardo Rebagliati Martins	Lima		Peru
9	Instituto Nacional de Salud del Niño - San Borja	Lima		Peru