TBI (Traumatic Brain Injury)Phase 3NCT05340803
Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter
A Phase 3 study testing Ultrasonograghic optic nerve sheath diameter US-ONSD, midazolam and dexmedetomidine in people with TBI (Traumatic Brain Injury), run by Assiut University.
Trial summary
In TBI, there is a strong correlation between increased ICP and bad outcome. So, appropriate monitoring can be the gold standard in management of TBI. ICP can be measured by invasive and noninvasive methds. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- TBI (Traumatic Brain Injury)
- What is being tested?
- Ultrasonograghic optic nerve sheath diameter US-ONSD, midazolam and dexmedetomidine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2022to 1 Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Middle age patients ( 18- 45 years old).
- Sever TBI (GCS < 8 and in need for mechanical ventilation).
- Stable hemodynamics
Who cannot join
- Age: younger than 18 or older than 45 years old.
- Mild and moderate TBI (GCS > 8).
- Shocked and hypoxic patients.
- Contraindications to dexmedetomidine as sever hypotension (mean arterial blood pressure < 60 mmHg), sever bradycardia (heart rate < 45 beat/min), and AV block in the group that will be sedated by midazolam and dexmedetomidine (group B).
- Adverse effects of dexmedetomidine in group B and need to stop it as sever hypotension (mean arterial blood pressure < 60 mmHg) , sever bradycardia (heart rate < 45 beat/min), and atrial fibrillation.
- Contraindications to magnesium sulfate as heart block, myocardial damage, hypermagnesemia and renal failure in the group that will be sedated by midazolam and magnesium sulfate (group C).
- Manifestations of magensium toxicity in group C and need to stop infusion if urine output < 80 mL in 4 hours, deep tendon reflexes are absent or serum magnesium level > 3.5 mmol/L .
Trial locations and contacts
No sites are listed yet.
Alshymaa Hassan Mohammed, Master contact
About this study
In TBI, there is a strong correlation between increased ICP and bad outcome. So, appropriate monitoring can be the gold standard in management of TBI. ICP can be measured by invasive and noninvasive methds. One of these noninvasive methods is bedside measurement of optic nerve sheath diameter (ONSD) by ocular ultrasonography
Read the detailed description
In the previous few years, agreat evidence has established for efficiency of dexmedetomidine (DEX) in management of TBI. Dexmedetomidine is a highly selective alpha-2 receptor agonist, its major sympatholytic and sedative actions are mediated primarily via reduced transmission in the locus coeruleus which is a part of the reticular activating system. It provides excellent sedation without respiratory depression, ease of arousability, and need not be stopped during weaning the patient from mechanical ventilation or for neurological assessment. It suits as an ideal sedative agent for patients with TBI. DEX has been shown to reduce cerebral ischemia/ reperfusion injury by suppressing inflammation, activating the anti-apoptotic signaling pathways, and inhibiting neuronal autophagy. Animal studies have shown that alpha-2 agonists are neuroprotective in craniocerebral and subarachnoid injuries but this has not been definitively shown in humans . The efficacy of DEX for sedation in intubated ICU patients is well established; however, its use in patients with TBI has not been comprehensively described .
Magnesium has shown great promise as a potential therapeutic agent in TBI during animal experiments . Magnesium is essential for the maintenance of cell membrane integrity, the stabilisation of genetic material and for a number of fundamental enzymatic reactions such as glycolysis, oxidative phosphorylation and protein synthesis, it is also known to act presynaptically to inhibit the release of excitatory amino acids, and be a non-competitive inhibitor of the voltage-gated N-methyl-D-aspartate (NMDA) receptor, an important link in the excitotoxic phase of secondary brain injury. As a consequence, magnesium's role in TBI has been of great interest to researchers.
- Conditions
- TBI (Traumatic Brain Injury)
- Being tested
- Ultrasonograghic optic nerve sheath diameter US-ONSD, midazolam, dexmedetomidine, magnesium sulfate
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasonograghic optic nerve sheath diameter US-ONSDRadiation
To compare effect of sedation in 3 groups by follow up of intracranial pressure by US-ONSD
midazolamDrug
midazolam
dexmedetomidineDrug
dexmedetomidine
magnesium sulfateDrug
magnesium sulfate
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Sedation by midazolam alone Receives: Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD; Drug: midazolam |
| Group B | Active comparator | Sedation by midazolam and dexmedetomidine during the first 24 hours Receives: Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD; Drug: midazolam; Drug: dexmedetomidine |
| Group C | Active comparator | Sedation by midazolam and magnesium sulfate during the first 24 hours Receives: Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD; Drug: midazolam; Drug: magnesium sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optic nerve sheath diameter (ONSD) changes by using ultrasound
ONSD is an indicator for changes in intracranial pressure in response to sedation with midazolam alone versus combination with dexmedetomidine or magnesium sulfate which group will show better control of the increased intracranial pressure to prevent secondary brain insults. ONSD of 5.8mm was used as cutoff point for identifying ICP above 20 mmHg.
Measured: up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start1 Nov 2022 (estimated)
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TBI (Traumatic Brain Injury)Studies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- To compare use of midazolam alone versus combination of midazolam with dexmedetomidine or magnesium sulfate in patients with sever TBI ( Glasgow Coma Scale \< 8 and in need for mechanical ventilation) as regards effect on ICP monitored by US-ONSD as the primary outcome and anti-inflammatory effect (neuroprotective effect) by measurement of serum IL-6 as a secondary outcome.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alshymaa Hassan Mohammed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05340803
- Sponsor's protocol ID
- ONSD for TBI patients
- Status last verified
- Apr 2022
- First submitted
- 17 Apr 2022
- Last updated
- 22 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter
- ClinicalTrials.gov ID
- NCT05340803
- Acronym / sponsor ID
- ONSD for TBI patients
- Conditions
- TBI (Traumatic Brain Injury)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Nov 2022 (estimated)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 22 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In TBI, there is a strong correlation between increased ICP and bad outcome. So, appropriate monitoring can be the gold standard in management of TBI. ICP can be measured by invasive and noninvasive methds. One of these noninvasive methods is bedside measurement of optic nerve sheath diameter (ONSD) by ocular ultrasonography
Detailed description
In the previous few years, agreat evidence has established for efficiency of dexmedetomidine (DEX) in management of TBI. Dexmedetomidine is a highly selective alpha-2 receptor agonist, its major sympatholytic and sedative actions are mediated primarily via reduced transmission in the locus coeruleus which is a part of the reticular activating system. It provides excellent sedation without respiratory depression, ease of arousability, and need not be stopped during weaning the patient from mechanical ventilation or for neurological assessment. It suits as an ideal sedative agent for patients with TBI. DEX has been shown to reduce cerebral ischemia/ reperfusion injury by suppressing inflammation, activating the anti-apoptotic signaling pathways, and inhibiting neuronal autophagy. Animal studies have shown that alpha-2 agonists are neuroprotective in craniocerebral and subarachnoid injuries but this has not been definitively shown in humans . The efficacy of DEX for sedation in intubated ICU patients is well established; however, its use in patients with TBI has not been comprehensively described .
Magnesium has shown great promise as a potential therapeutic agent in TBI during animal experiments . Magnesium is essential for the maintenance of cell membrane integrity, the stabilisation of genetic material and for a number of fundamental enzymatic reactions such as glycolysis, oxidative phosphorylation and protein synthesis, it is also known to act presynaptically to inhibit the release of excitatory amino acids, and be a non-competitive inhibitor of the voltage-gated N-methyl-D-aspartate (NMDA) receptor, an important link in the excitotoxic phase of secondary brain injury. As a consequence, magnesium's role in TBI has been of great interest to researchers.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- To compare use of midazolam alone versus combination of midazolam with dexmedetomidine or magnesium sulfate in patients with sever TBI ( Glasgow Coma Scale < 8 and in need for mechanical ventilation) as regards effect on ICP monitored by US-ONSD as the primary outcome and anti-inflammatory effect (neuroprotective effect) by measurement of serum IL-6 as a secondary outcome.
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD, Drug: midazolamSedation by midazolam alone |
| Group B | Active comparator | Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD, Drug: midazolam, Drug: dexmedetomidineSedation by midazolam and dexmedetomidine during the first 24 hours |
| Group C | Active comparator | Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD, Drug: midazolam, Drug: magnesium sulfateSedation by midazolam and magnesium sulfate during the first 24 hours |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Middle age patients ( 18- 45 years old).
- Sever TBI (GCS < 8 and in need for mechanical ventilation).
- Stable hemodynamics
Key exclusion criteria (7 listed)
- Age: younger than 18 or older than 45 years old.
- Mild and moderate TBI (GCS > 8).
- Shocked and hypoxic patients.
- Contraindications to dexmedetomidine as sever hypotension (mean arterial blood pressure < 60 mmHg), sever bradycardia (heart rate < 45 beat/min), and AV block in the group that will be sedated by midazolam and dexmedetomidine (group B).
- Adverse effects of dexmedetomidine in group B and need to stop it as sever hypotension (mean arterial blood pressure < 60 mmHg) , sever bradycardia (heart rate < 45 beat/min), and atrial fibrillation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ultrasonograghic optic nerve sheath diameter US-ONSDTo compare effect of sedation in 3 groups by follow up of intracranial pressure by US-ONSD | Radiation | Group A, Group B, Group C |
| midazolammidazolam | Drug | Group A, Group B, Group C |
| dexmedetomidinedexmedetomidine | Drug | Group B |
| magnesium sulfatemagnesium sulfate | Drug | Group C |
Primary outcome
Optic nerve sheath diameter (ONSD) changes by using ultrasound
Time frame: up to 24 hours
ONSD is an indicator for changes in intracranial pressure in response to sedation with midazolam alone versus combination with dexmedetomidine or magnesium sulfate which group will show better control of the increased intracranial pressure to prevent secondary brain insults. ONSD of 5.8mm was used as cutoff point for identifying ICP above 20 mmHg.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alshymaa Hassan Mohammed, Master contact
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ultrasonograghic optic nerve sheath diameter US-ONSD, midazolam and dexmedetomidine in people with TBI (Traumatic Brain Injury), run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alshymaa Hassan Mohammed, Master (01067555351 ext. 01154278436, Alshimaa.hassan@medicine.luxor.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optic nerve sheath diameter (ONSD) changes by using ultrasound (time frame: up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.