Comparing Sedatives for Intracranial Pressure Control in Traumatic Brain Injury

NCT07678216 | Not Yet Recruiting

• 1 other identifier: 1230/3/26
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the effects of propofol, midazolam, and dexmedetomidine on intracranial pressure control and clinical outcomes in adults with moderate-to-severe traumatic brain injury undergoing urgent neurosurgical intervention. The main questions it aims to answer are:

• Which sedative agent provides better control of intracranial pressure, assessed by optic nerve sheath diameter (ONSD), during the first 24 hours after neurosurgical intervention?
• How do the three sedative agents compare in achieving target sedation depth, maintaining hemodynamic stability, and improving short-term clinical outcomes such as ICU mortality, duration of mechanical ventilation, and ICU length of stay? Participants will be randomly assigned to receive propofol, midazolam, or dexmedetomidine for 24 hours of continuous sedation. Clinical, hemodynamic, and neurological outcomes will be assessed and compared among the three study groups.

Conditions

Moderate-to-Severe Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Intracranial Pressure Control Assessed by Optic Nerve Sheath Diameter (ONSD)

  Intracranial pressure control will be evaluated using serial optic nerve sheath diameter (ONSD) measurements obtained by ocular ultrasonography. The primary outcome will be the mean ONSD over the 24-hour intervention period, analyzed as a continuous measure of intracranial pressure control.

  Baseline, 6 hours, 12 hours, and 24 hours after initiation of sedation

Secondary Outcomes (11)

• Proportion of Time at Target Sedation Level

  24 hours after initiation of sedation

• Mean Richmond Agitation-Sedation Scale (RASS) Score

  24 hours after initiation of sedation

• Need for Rescue Sedation

  24 hours after initiation of sedation

• Time to Achieve Target Sedation

  24 hours after initiation of sedation

• Incidence of Hypotension

  24 hours after initiation of study sedation

Study Arms (3)

Propofol

EXPERIMENTAL

Participants receive continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated to 1-4 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.

Drug: propofol

Midazolam

EXPERIMENTAL

Participants receive continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated to 0.02-0.1 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.

Drug: midazolam

dexmedetomidine

EXPERIMENTAL

Participants receive continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated to 0.2-0.7 μg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.

Drug: Dexmedetomidine

Interventions

propofol DRUG

Continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated within a range of 1-4 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period.

Propofol

midazolam DRUG

Continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated within a range of 0.02-0.1 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period. An initial bolus dose of 0.05 mg/kg may be administered if rapid sedation is required.

Midazolam

Dexmedetomidine DRUG

Continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated within a range of 0.2-0.7 μg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period. No loading dose will be administered.

dexmedetomidine

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Moderate to severe traumatic brain injury with post-resuscitation Glasgow Coma Scale (GCS) ≤12
• Undergone urgent neurosurgical intervention (craniotomy, craniectomy, or ICP monitor placement) within 24 hours of injury
• Admitted to ICU and expected to require continuous sedation
• Hemodynamically stable or stabilized (defined as MAP ≥65 mmHg with vasopressor requirement ≤0.1 mcg/kg/min norepinephrine equivalent)
• Informed consent obtained from legally authorized representative

You may not qualify if:

• The Relative refusal to participate in the research.
• Known allergy or contraindication to propofol, midazolam, or dexmedetomidine
• Pre-existing neurological disorders (epilepsy, prior stroke, brain tumors, dementia) that may interfere with outcome assessment
• Severe hepatic dysfunction (Child-Pugh Class C) or acute liver failure
• Severe renal dysfunction (eGFR \<30 mL/min/1.73m² or requiring renal replacement therapy)
• Pregnancy or breastfeeding
• Hemodynamic instability requiring norepinephrine \>0.1 mcg/kg/min or equivalent vasopressor support
• Heart rate \<50 bpm or second/third-degree AV block without pacemaker (relative contraindication for dexmedetomidine)
• Clinical determination of brain death or expected survival \<24 hours
• Enrollment in another interventional trial
• Severe polytrauma requiring ongoing surgical interventions that would interfere with protocol adherence

Sponsors & Collaborators

• Aswan University: lead

Study Sites (1)

Aswan University Hospital

Asyut, Asyut Governorate, 81528, Egypt

Location

MeSH Terms

Interventions

Propofol; Midazolam; Dexmedetomidine

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Ahmed Elsaied Aly, Ph.D.

  Sohag University

  STUDY CHAIR

Central Study Contacts

Mohamed Abdelhamed, M.Sc

CONTACT

+201061651065; mohamed.said@med.aswu.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is an open-label randomized trial. Treating clinicians and investigators are aware of treatment allocation. Outcome assessment is blinded; optic nerve sheath diameter (ONSD) measurements are performed by a blinded ultrasonographer, and radiological outcomes are evaluated by a blinded neuroradiologist who is unaware of treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecture

Model Details: Participants will be randomly assigned in a 1:1:1 ratio to one of three parallel treatment groups receiving continuous sedation for 24 hours following urgent neurosurgical intervention for moderate-to-severe traumatic brain injury. Group A will receive propofol initiated at 1 mg/kg/h and titrated within a range of 1-4 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4. Group B will receive midazolam initiated at 0.03 mg/kg/h and titrated within a range of 0.02-0.1 mg/kg/h to maintain the target RASS score. An initial bolus dose of 0.05 mg/kg may be administered if rapid sedation is required. Group C will receive dexmedetomidine initiated at 0.4 μg/kg/h and titrated within a range of 0.2-0.7 μg/kg/h to maintain the target RASS score. Participants will remain in their assigned treatment group throughout the intervention period, and outcomes will be compared between groups. The trial uses a prospective randomized parallel-group design with blinded

Study Record Dates

• First Submitted: June 20, 2026
• First Posted: July 1, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)