Optimización de oxígeno cerebral en TBI grave, fase 3 (BOOST3)
Optimización de oxígeno cerebral en TBI grave (BOOST3): un estudio de eficacia comparativa para probar la eficacia de un protocolo de tratamiento prescrito basado en el control de la presión parcial de oxígeno del tejido cerebral.
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU). The study will determine the safety and efficacy of a strategy guided by treatment goals based on both intracranial pressure (ICP) and brain tissue oxygen (PbtO2) as compared to a strategy guided by treatment goals based on ICP monitoring alone. Both of these alternative strategies are used in standard care. It is unknown if one is more effective than the other. In both strategies the monitoring and goals help doctors adjust treatments including the kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. The results of this study will help doctors discover if one of these methods is more safe and effective.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU).
When a person has a TBI, their injured brain can swell over a period of hours or days. If the brain swells too much, the pressure in the skull increases and becomes dangerous, causing further injury to the brain. To try to prevent this, doctors usually insert a device, an ICP monitor, into the brain through a hole in the skull of people with severe TBI. An ICP monitor measures the pressure inside the skull. Most doctors agree that it is important to measure and prevent high ICP. Patients with injured brains also suffer additional injury to the brain if the amount of oxygen in the brain gets too low. Some doctors also insert a second device, a PbtO2 monitor, in the brain through the same or a second hole in the skull to measure brain tissue oxygen. A PbtO2 monitor measures how much oxygen is in a small area of the brain near the tip of the monitor. Other doctors think this is unnecessary and unhelpful. Both monitoring devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with TBI. Both are commonly used. The ICP and PbtO2 goals guided by these monitors are used to help doctors adjust their treatment choices. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. Each of these treatment decisions is intended to improve outcomes. However, each treatment decision also involves potential risks. Different treatment decisions may result in different risks. This study will also help doctors better understand these risks. This study is funded by the National Institutes of Health because it answers questions important to the care of patients with TBI.
This study is a two-arm, single-blind, randomized, controlled, phase III, multi-center trial of ICU monitoring and treatment strategies for patients with severe TBI. It will compare the efficacy of ICU care guided by PbtO2 and ICP monitoring versus monitoring of ICP alone in the first 5 days after injury. Only subjects who have severe TBI and require invasive monitoring, according to Brain Trauma Foundation (BTF) and American College of Surgeons-Trauma Quality Improvement (ACS TQIP) guidelines, will be enrolled. All participants in this study will have both ICP monitors and PbtO2 monitors. Half of the participants will be randomized to an arm that includes treatment informed by PbtO2 and ICP, and half will be randomized to an arm that treats only ICP.
The PbtO2 values of those in the ICP only arm will be masked, so that the treating physicians will not be guided by PbtO2 information. Participants in the PbtO2 and ICP arm will have PbtO2 monitored and low measurements treated. Treatments to address physiological goals in both arms will follow a clinical standardization plan. Participants will be followed for 6 months and occurrence of serious adverse events or death will be recorded. Participants will have a follow-up interview to assess their level of recovery approximately 6 months post injury.
To reduce the likelihood of imbalance of important prognostic factors between groups, a covariate-adjusted randomization scheme will be used in this study. Adjustment variables are clinical site and probability of a poor outcome as defined by the IMPACT core model.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Montreal, Canadá, H4J 1C5
- CIUSSS-NIM Hopital du Sacre - Coeur de Montreal
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Alberta
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Calgary, Alberta, Canadá, T2N 2T9
- University of Calgary - Foothills Medical Centre
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Ontario
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Toronto, Ontario, Canadá, M5B 1W8
- St. Michaels Hospital
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California
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Los Angeles, California, Estados Unidos, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Estados Unidos, 90095-7436
- Ronald Reagan UCLA Medical Center
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Palo Alto, California, Estados Unidos, 94305
- Stanford University Medical Center
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Sacramento, California, Estados Unidos, 95817
- UC Davis Medical Center
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San Francisco, California, Estados Unidos, 94143
- San Francisco General Hospital
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- University of Colorado Hospital
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06510
- Yale New Haven Hospital
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Florida
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Gainesville, Florida, Estados Unidos, 32608
- UF Health Shands Hospital
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Georgia
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Atlanta, Georgia, Estados Unidos, 30303
- Grady Memorial Hospital
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Hawaii
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Honolulu, Hawaii, Estados Unidos, 96813
- The Queen's Medical Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago Medical Center
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46260
- St. Vincent Hospital
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Maine
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Portland, Maine, Estados Unidos, 04102
- Maine Medical Center
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- Johns Hopkins Hospital
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland Medical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, Estados Unidos, 02128
- Massachusetts General Hospital
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Worcester, Massachusetts, Estados Unidos, 01655
- UMASS Memorial Medical Center
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Detroit Receiving Hospital
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Detroit, Michigan, Estados Unidos, 48201
- Henry Ford Hospital
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Minnesota
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Saint Paul, Minnesota, Estados Unidos, 55101
- Regions Hospital
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New Jersey
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Camden, New Jersey, Estados Unidos, 08103
- Cooper University Hospital
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New Mexico
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Albuquerque, New Mexico, Estados Unidos, 87131
- University of New Mexico Hospital
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New York
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Flushing, New York, Estados Unidos, 11355
- NewYork-Presbyterian Queens Hospital
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Manhasset, New York, Estados Unidos, 11030
- North Shore University Hospital
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New York, New York, Estados Unidos, 10032
- NYP Columbia University Medical Center
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Rochester, New York, Estados Unidos, 14642
- Strong Memorial Hospital
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Syracuse, New York, Estados Unidos, 13210
- SUNY Upstate Medical University
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The Bronx, New York, Estados Unidos, 10461
- Jacobi Medical Center
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27514
- University of North Carolina Medical Center
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Hospital
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45219
- University of Cincinnati Medical Center
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Columbus, Ohio, Estados Unidos, 43214
- Riverside Methodist Hospital
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Columbus, Ohio, Estados Unidos, 43210
- OSU Wexner Medical Center
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health & Science University Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Penn Presbyterian Medical Center
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Pittsburgh, Pennsylvania, Estados Unidos, 15212
- UPMC Presbyterian Hospital
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Texas
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Dallas, Texas, Estados Unidos, 75235
- Parkland Hospital
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Houston, Texas, Estados Unidos, 77030
- Ben Taub General Hospital
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San Antonio, Texas, Estados Unidos, 78229
- University of Texas Health Science Center San Antonio
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- University of Utah Healthcare
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Virginia
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Richmond, Virginia, Estados Unidos, 23298
- VCU Medical Center
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Washington
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Seattle, Washington, Estados Unidos, 98104
- Harborview Medical Center
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West Virginia
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Morgantown, West Virginia, Estados Unidos, 26506
- WVU Healthcare Ruby Memorial Hospital
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Froedtert Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Non-penetrating traumatic brain injury
- Glasgow Coma Scale (GCS) 3-8 measured off paralytics
- Glasgow Coma Scale motor score < 6 if endotracheally intubated
- Evidence of intracranial trauma on CT scan
- Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
- Able to place intracranial probes and randomize within 12 hours from injury
- Age greater than or equal to 14 years
Exclusion Criteria:
- Non-survivable injury
- Bilaterally absent pupillary response in the absence of paralytic medication
- Contraindication to the placement of intracranial probes
- Treatment of brain tissue oxygen values prior to randomization
- Planned use of devices which may unblind treating physicians to brain tissue hypoxia
- Systemic sepsis at screening
- Refractory hypotension
- Refractory systemic hypoxia
- PaO2/FiO2 ratio < 150
- Known pre-existing neurologic disease with confounding residual neurological deficits
- Known inability to perform activities of daily living (ADL) without assistance prior to injury
- Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
- Pregnancy
- Prisoner
- On EFIC Opt-Out list as indicated by a bracelet or medical alert
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: ICP only
ICP guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP) caused by a swollen brain. This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury. |
In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull, but PbtO2 is not used to guide care. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada, and are routinely used in patients with severe TBI. Doctors adjust their treatment choices to try to achieve this ICP goal. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study. |
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Comparador activo: ICP + PbtO2
ICP + PbtO2 guided management strategy: Care in the ICU of research participants randomized to this arm will be guided by a monitoring and treatment strategy in which doctors try to prevent high intracranial pressure (ICP), and also try to prevent low PbtO2 (brain tissue oxygen levels). This strategy is one of two alternative strategies that is currently used in standard care of patients with traumatic brain injury. |
In this management strategy, the physiological goal is to avoid ICP from exceeding 22 mm Hg and to avoid PbtO2 dropping below 20 mm Hg. ICP and PbtO2 are monitored using devices inserted into the brain through a hole in the skull. These devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with severe TBI. The devices are used in standard care at hospitals participating in this research study. Doctors adjust their treatment choices to try to achieve these ICP and PbtO2 goals. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. This management strategy is used to guide care for 5 days in this research study. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Glasgow Outcome Scale-Extended (GOS-E)
Periodo de tiempo: 6 months
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The Glasgow Outcome Scale-Extended (GOS-E) is a global scale for functional outcome, in which higher scores indicate better outcomes. The GOS-E rates patient status into one of eight categories. A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. All injury related disabilities are assessed. |
6 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Survival
Periodo de tiempo: At discharge from hospital, an average of 19 days
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Survival at discharge from hospital |
At discharge from hospital, an average of 19 days
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Total Brain Hypoxia Exposure
Periodo de tiempo: Inclusive of up to 5 days of study intervention
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The cumulative area on the time versus brain tissue oxygenation (PbtO2) curve in which PbtO2 is less than 20 mmHg. |
Inclusive of up to 5 days of study intervention
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Cognition: Rey Auditory Verbal Learning Test
Periodo de tiempo: 6 months
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A measure of verbal learning and memory. |
6 months
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Cognition: Trail Making Test Part A+B
Periodo de tiempo: 6 months
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A measure of attention, visual-motor tracking and executive functioning. |
6 months
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Emotional Health: Rivermead Post-Concussion Symptom Questionnaire
Periodo de tiempo: 6 months
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A measure of the presence and severity of post-concussion somatic, cognitive, and emotional symptoms. |
6 months
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Emotional Health: Brief Symptom Inventory 18
Periodo de tiempo: 6 months
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A measure of psychological distress and psychiatric disorders. |
6 months
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Emotional Health: Satisfaction with Life Scale
Periodo de tiempo: 6 months
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A measure of global cognitive judgments of one's life satisfaction. |
6 months
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Functional Status Exam
Periodo de tiempo: 6 months
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Change in the activities of every day life as a function of a sudden event or illness |
6 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Lori Shutter, MD, University of Pittsburgh, Pittsburgh, PA 15260
- Investigador principal: Ramon Diaz-Arrastia, MD, PhD, University of Pennsylvania, Philadelphia, PA 19104
- Investigador principal: William Barsan, MD, University of Michigan, Ann Arbor, MI 48109
- Investigador principal: Sharon Yeatts, PhD, Medical University of South Carolina, Charleston, SC 29425
Publicaciones y enlaces útiles
Publicaciones Generales
- Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C, Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017 Nov;45(11):1907-1914. doi: 10.1097/CCM.0000000000002619.
- Bernard F, Barsan W, Diaz-Arrastia R, Merck LH, Yeatts S, Shutter LA. Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone. BMJ Open. 2022 Mar 10;12(3):e060188. doi: 10.1136/bmjopen-2021-060188.
- Fiore M, Bogossian E, Creteur J, Oddo M, Taccone FS. Role of brain tissue oxygenation (PbtO2) in the management of subarachnoid haemorrhage: a scoping review protocol. BMJ Open. 2020 Sep 15;10(9):e035521. doi: 10.1136/bmjopen-2019-035521.
- Steinberg A, Case N, Yang Y, Fischhoff B, Callaway CW, Coppler PJ, Barsan WG, Diaz-Arrastia R, Geocadin R, Okonkwo DO, Shutter L, Silbergleit R, Meurer WJ, Yeatts SD, Elmer J. Clinicians' Approaches to Prognostication After Traumatic Brain Injury and Cardiac Arrest: A Multi-Hospital, Qualitative Study. Neurocrit Care. 2026 Aug;45(1):132-141. doi: 10.1007/s12028-026-02452-z. Epub 2026 Feb 12.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Heridas y Lesiones
- Signos y Síntomas Respiratorios
- Trauma craneoencefálico
- Trauma, Sistema Nervioso
- Lesiones Cerebrales
- Hipoxia
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Lesiones Cerebrales Traumáticas
- Hipoxia, Cerebro
Otros números de identificación del estudio
- BOOST3
- U01NS099046 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Marco de tiempo para compartir IPD
1 year after publication on main outcome results paper
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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