The Impact and Outcomes of Combined Cerebrolysin and Amantadine Sulfate Administration on Management of Patients With Traumatic Brain Injury in the ICU
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Ain Shams University
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- The Glasgow Coma Scale (GCS)
Study Overview
Brief Summary
The goal of this interventional study is to Measure the potential benefits of combined administration of cerebrolysin and amantadine sulfate as an add-on therapy to the standard management of patients admitted to the ICU with traumatic brain injury.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age between 18 and 70 years.
- •Clinical diagnosis of head injury with moderate to severe TBI and a Glasgow coma scale (GCS) score of 7-12 at the time of hospital admission.
- •Pre-hospital intubation/sedation/paralysis was accepted if the GCS score had been assessed before intubation/sedation/paralysis by trained staff.
Exclusion Criteria
- •History of intracranial interventions as well as ischemic or hemorrhagic stroke.
- •Any neurological or non-neurological condition independent from TBI that might influence the functional outcome or other efficacy outcome measures.
- •Clear clinical signs of intoxication influencing the evaluation, in the investigator's judgment.
- •Patients with penetrating brain injury.
- •Pregnancy or lactation.
- •Patient with sever renal impairment (creatinine clearance > 30 ml/ minute).
Arms & Interventions
standard of care + Cerebrolysin
patients receiving the standard protocol of management of head injury in the ICU plus 2 cycles of Cerebrolysin , each cycle 10 days, for total 20 days. From day 1 to day 10: cerebrolysin 50 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes. From day 21-30 : cerebrolysin 20 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes.
Intervention: Cerebrolysin (Drug)
standard of care + Cerebrolysin + Amantadine sulfate
patients receiving the standard protocol of management of head injury in the ICU plus amantadine sulfate at a dose of 100 mg twice daily on the day after randomization, with this dose will be continued for 14 days. The dose will be increased to 150 mg twice daily at week 3 and to 200 mg twice daily at week 4 (total 4 weeks), combined with 2 cycles of Cerebrolysin , each cycle 10 days, for total 20 days. From day 1 to day 10: cerebrolysin 50 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes. From day 21-30 : cerebrolysin 20 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes.
Intervention: Cerebrolysin (Drug)
standard of care + Cerebrolysin + Amantadine sulfate
patients receiving the standard protocol of management of head injury in the ICU plus amantadine sulfate at a dose of 100 mg twice daily on the day after randomization, with this dose will be continued for 14 days. The dose will be increased to 150 mg twice daily at week 3 and to 200 mg twice daily at week 4 (total 4 weeks), combined with 2 cycles of Cerebrolysin , each cycle 10 days, for total 20 days. From day 1 to day 10: cerebrolysin 50 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes. From day 21-30 : cerebrolysin 20 ml once daily diluted in 250 ml normal saline intravenous infusion over 15 minutes.
Intervention: amantadine sulfate (Drug)
Outcomes
Primary Outcomes
The Glasgow Coma Scale (GCS)
Time Frame: Glasgow coma scale (GCS) will be recorded on admission, and every week up to 6 weeks of trauma to detect the improvement in level of consciousness after management in all groups.
The Glasgow Coma Scale (GCS) is used to assess the level of consciousness. It depends on the best motor, verbal and eye opening responses. GCS is used to classify insult severity as minor \[GCS 13-15\], moderate \[GCS 9-12\] and severe \[GCS 3-8\].
Disability rating-scale for severe head trauma (DRS)
Time Frame: DRS score will be collected at baseline and weekly through week 6 (during 4 weeks of treatment and 2 weeks after discontinuation).
Disability rating-scale for severe head trauma (DRS) includes measures of arousability, awareness and responsivity of eye opening, verbalization, and motor response; cognitive ability of for Self Care Activities: understanding of feeding, dressing, and grooming; degree of assistance and supervision required; and employability. Scores range from 0 to 29, with higher values indicating greater disability.
Coma Recovery Scale-Revised (CRS-R)
Time Frame: CRS-R will be compared over the 4 weeks of treatment and during 2-weeks after discontinuation of treatment
Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment tool comprising six organized subscales (i.e., auditory, visual, motor, oro-motor,verbal, communication, and arousal); scores range from 0 to 23, with higher scores indicating a higher level of neurobehavioral function.
The Glasgow Outcome Scale (GOS)
Time Frame: atients in all groups will be assessed with The Glasgow Outcome Scale (GOS) on the end of 6th week.
The Glasgow Outcome Scale (GOS) is one of the most widely used outcome instruments to assess global disability and recovery after traumatic brain injury. Patients in all groups will be assessed with The Glasgow Outcome Scale (GOS) on the end of 6th week which classify patients into: dead, vegetative state, severe disability, moderate disability and good recovery.
Secondary Outcomes
No secondary outcomes reported
Investigators
ragab elshabasy
Principal Investigator
Ain Shams University