Trial Information

Traumatic Brain Injury in Latin America: Lifespan Analysis

The objective of this application is to establish a network of Centers of Excellence within
LABIC that will, in collaboration with U.S. partners, conduct research and training programs
about TBI. To that end, this project will include scientific investigation and capacity
building.

The primary focus for scientific investigation is to conduct a high quality randomized
controlled trial addressing a question of critical importance to the management of TBI
worldwide:

• Does the use of information provided by intracranial pressure (ICP) monitoring to direct
treatment of patients with TBI improve medical practice and patient outcomes in a developing
country? This trial will be conducted in three trauma centers in Bolivia, in which the
infrastructures and practice patterns are optimal for strong internal validity, while at the
same time the level of resources is representative of trauma care as practiced in the
developing world.

The secondary focus for scientific investigation is to conduct a prospective study of TBI in
seven trauma centers in Bolivia, Brazil, Argentina, Colombia, and Ecuador that represent the
variation in access to and use of resources in the developing world. This study will
address two questions of vital importance to management of TBI in developing countries:

- To what extent do the findings from the randomized trial about ICP monitoring in
particular, and brain injury care in general, generalize to diverse populations of TBI
patients in Latin America?

- What is the association between resources and outcomes from TBI in developing
countries? To build capacity, we will provide education, equipment, and structure, and
will foster the collaborations established during the pilot R21 phase of this project.
Our commitment is that LABIC becomes completely independent as a research entity. At
the end of the funding period LABIC constituents will be able to identify important
research questions, design the research, write successful proposals for funding, carry
out strong studies, analyze and interpret the data, submit successful publications to
internationally recognized peer reviewed journals, and disseminate information across
Latin America.

Our specific aims are:

Specific Aim#1: In a randomized controlled trial in 3 trauma centers in Bolivia, test the
effect on outcomes of management of severe TBI guided by information from ICP monitors vs. a
standard empiric protocol.

Hypothesis #1: Patients with severe TBI whose acute care treatment is managed using ICP
monitors will have significantly lower mortality and better neuropsychological and
functional recovery at 6 months post-trauma than those whose treatment is managed with the
standard protocol.

Hypothesis #2: The incorporation of ICP monitoring into the care of patients with severe
TBI will minimize secondary complications and decrease length of stay in intensive care unit
(ICU).

Specific Aim #2: In a prospective, observational study conducted in trauma centers in Latin
America, test the association between resource availability/medical management and outcomes
for patients with severe TBI.

Hypothesis #3: The association between treatment and outcomes for patients with severe TBI
identified in the randomized trial of ICP monitoring will generalize to the population in
the prospective, observational, multi-center, multi-national study.

Hypothesis #4: Variations in resource availability and medical management will be
significantly associated with mortality and functional recovery for patients with severe
TBI, after controlling for patient and injury characteristics.

Specific Aim #3: Establish a network of research centers with investigators trained and
skilled in the design, conduct, and funding of research programs to address TBI and other
brain disorders in Latin America.

In fulfilling these aims, we will answer important research questions about patient
characteristics, treatment, and outcomes from TBI in an environment of limited resources,
aspects of which will generalize to other developing countries as well as to the developed
world. In a developing country, we will test the effectiveness of technology considered
pivotal to brain trauma treatment in the developed world - the ICP monitor. The outcome of
this trial may serve to standardize practice, improve outcomes, and mobilize resources
worldwide. A randomized controlled trial of ICP monitoring has never been performed. As
specifically stated in the Guidelines for the Management of Severe Brain Injury (Bullock et
al., 1996), this is a critical gap in the evidence base that supports the role of ICP
monitoring in TBI care. As such, the results of the RCT as performed in Bolivia will have
global implications regardless of the level of development of the trauma system.

We will also establish sustainable capacity to conduct research about TBI in Latin America.
Within the structure of LABIC, we will create a cadre of professionals who are trained in
clinical research and equipped to carry out studies that answer questions important to Latin
America. These studies will establish a literature base from which Latin American treatment
guidelines will be generated. With training in cognitive assessment, we will introduce a
new discipline into many of the Latin American medical systems that will provide an
understanding of the unique and profound disabilities associated with brain disorders.