Combined Cerebrolysin and Amantadine Sulfate Administration for Patients With Traumatic Brain Injury in the ICU

NCT06052787 | Completed Phase 3 DMC

• 1 other identifier: pharmacotherapy in TBI in ICU
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (4)

• The Glasgow Coma Scale (GCS)

  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 \[GCS 3-8\].

  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.

• Disability rating-scale for severe head trauma (DRS)

  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.

  DRS score will be collected at baseline and weekly through week 6 (during 4 weeks of treatment and 2 weeks after discontinuation).

• Coma Recovery Scale-Revised (CRS-R)

  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.

  CRS-R will be compared over the 4 weeks of treatment and during 2-weeks after discontinuation of treatment

• The Glasgow Outcome Scale (GOS)

  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.

  atients in all groups will be assessed with The Glasgow Outcome Scale (GOS) on the end of 6th week.

Study Arms (3)

standard of care

NO INTERVENTION

patients receiving the standard protocol of management of head injury in the ICU including * Ventilatory support, sedation and analgesia. * Hemodynamic support. * Hyperosmolar therapy. * Early post traumatic seizure prophylaxis. * Nutritional support: will try to start enteral feeds as soon as possible or total parenteral * nutrition will be used in the case of enteral feeding intolerance. * Temperature management: to maintain normothermia * Glycemic control: to maintain a glucose level of \[140 -180 mg/dl\] * Peptic ulcer prophylaxis: * Deep venous thrombosis (DVT) prophylaxis

standard of care + Cerebrolysin

EXPERIMENTAL

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.

Drug: Cerebrolysin

standard of care + Cerebrolysin + Amantadine sulfate

EXPERIMENTAL

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.

Drug: Cerebrolysin; Drug: amantadine sulfate

Interventions

Cerebrolysin DRUG

Cerebrolysin, a mixture of free amino acids and low molecular weight peptides, has a neurotrophic factor-like activity with immediate pleiotropic neuroprotective activity and long-term multimodal effects on endogenous post-lesional regulation. Cerebrolysin has been suggested to exert beneficial effects on neurobehavioural functions, cognitive performance , and neuro-motor recovery , as part of initial therapy in severe and moderate acute TBI.

standard of care + Cerebrolysin; standard of care + Cerebrolysin + Amantadine sulfate

amantadine sulfate DRUG

The dopaminergic agonist amantadine enhances presynaptic dopamine release and inhibits dopamine reuptake, resulting in an increased amount of dopamine in the synaptic cleft. Amantadine may also increase the density of postsynaptic dopamine receptors and alter the conformation of these receptors. Amantadine acts as an NMDA receptor antagonist, blocking glutamate, an NMDA channel activator. This effect may be responsible for amantadine's possible beneficial effect soon after TBI

Also known as: PK-MERZ

standard of care + Cerebrolysin + Amantadine sulfate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of medicine - Ain shams university

Cairo, Egypt

Location

Related Publications (17)

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  BACKGROUND

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• Talsky A, Laura R. Pacione, Tammy Shaw, Lori Wasserman, Adam Lenny, Amol Verma, Gillian Hurwitz, Robyn Waxman, Andrew Morgan, Shree Bhalerao .(2011).Pharmacological interventions for traumatic brain injury. BC Med J; 53:26-31

  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

cerebrolysin; Amantadine

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Ragab D Elshabasy

  faculty of medicine - Ain shams university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: September 25, 2023
• Study Start: September 1, 2023
• Primary Completion: May 30, 2025
• Study Completion: August 1, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)