Sixty-nine million individuals worldwide are estimated to sustain a TBI each year. The
proportion of TBIs resulting from road traffic collisions was greatest in Africa and
Southeast Asia (both 56%) and lowest in North America (25%).
Head injury remains the leading cause of death and severe disability in young adults, and
it is also the most important single injury contributing to traumatic mortality and
morbidity.
Traumatic brain injury (TBI) is a non-degenerative, non-congenital insult to the brain
from an external mechanical force, possibly leading to permanent or temporary impairment
of cognitive, physical, and psychosocial functions, with an associated diminished or
altered state of consciousness.
There is growing evidence that medications may speed recovery by enhancing some
neurological functions without impacting others. Pharmacotherapy is increasingly being
used in both the sub-acute (less than 1 month post-TBI) and chronic (more than 1 month
post-TBI) phases.
Amantadine is known to enhance neurotransmission, through the activation of
dopamine-dependent brain circuits, and increases dopamine activity in pre-synapses and
post- synapses, acting as an antagonist of the N-methyl D-aspartate receptor.
A study done on 184 patients of severe traumatic brain injury found better οutϲοme in the
treatment group with amantadine sulfate as compared with the plaϲeƅο group over the
4-week treatment interval, and they demonstrated that amantadine improved recovery in
patients with moderate and severe TBI.
Giaϲinο et al. used amantadine in 184 patients for 4 to 16 weeks after TBI, They found
that Amantadine accelerated the pace of functional recovery during active treatment in
patients with post-traumatic disorders of consciousness.
Cerebrolysin is a peptide preparation produced by a biotechnological process, a
standardized enzymatic breakdown of purified, lipid-free brain proteins, a
pharmacological agent with neuro-restorative and neuro-protective effects. It stimulates
neuronal survival and differentiation, axonal growth and sprouting, the formation of new
synapses, and neurogenesis in the dentate gyrus.
El Sayed et al. published a meta-analysis of the effect of different neuroprotective
drugs in management of patients with traumatic brain injury resulting in substantial
superiority of the cerebrolysin that was reflected in three-fold cognitive improvement
and favorable Glasgow outcome score.
In a prospective, randomized, double-blind, placebo-controlled, parallel-group,
multi-center phase IIIb/IV trial, the CAPTAIN I trial registered beneficial effects of
Cerebrolysin after moderate to severe TBI.
The CAPTAIN II trial, enrolled 142 patients with moderate to severe TBI in a
single-center, prospective, randomized, double-blind, placebo-controlled clinical trial
confirms the benefits of Cerebrolysin in moderate to severe TBI.
In their retrospective case -control study, Lee et al., identified that an
amantadine-plus-cerebrolysin regimen was shown to additively affect the conscious state
of patients with prolonged disturbed consciousness secondary to acute brain injury,
especially in patients who remained in a prolonged vegetative state.
Type of the Study: a single-center, prospective, randomized, double-blinded
(Patients, healthcare providers, data collectors, and outcome assessors are blinded
to treatment allocation), and phase III clinical trial.
Study setting: The study will be conducted at Ain Shams university hospitals.
Study period: The study will be conducted over 18-24 months.
Study population: patients admitted to the ICU with traumatic brain injury who are
eligible according to the inclusion and exclusion criteria.
sample size : 150 patients in three groups , 50 patients in each group.
Study procedures:
All selected patients fulfilling the inclusion criteria will be subjected to the
following on admission:
Formal written consent from patient relatives.
Clinical data of all patients will be recorded in the admission sheets of ICU, these
data includes: Demographic characteristics, etiology of trauma ,GCS ,vital signs
(mean arterial blood pressure (MAP), heart rate, oxygen saturation)
,electrocardiogram (ECG), Pupil (size, reactivity and if symmetrical or not) and any
other body trauma as bone fractures, chest trauma ,etc.
The imaging findings: CT will be done to all patients on admission to ICU to detect
the basal pathological lesions as brain edema, hemorrhagic contusions, extradural
hemorrhage, and subdural hemorrhage.
The patients of the study will be randomly allocated into three groups.
