Brain EdemaPhase 4NCT03573999
Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation
A Phase 4 study testing Mannitol and NaCl 7.5% in people with Brain Edema and Metabolic Disturbance, run by Aristotle University Of Thessaloniki at 2 sites in Greece.
Trial summary
Usage of osmotic agents is a standard practice in neuroanesthesia since cerebral edema is a very common situation for patients with pathology in the brain. Cerebral edema is defined as the accumulation of fluid in the intracellular or extracellular compartments of the brain. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Brain Edema, Metabolic Disturbance, Electrolyte and Fluid Balance Conditions
- What is being tested?
- Mannitol and NaCl 7.5%
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesGreece
- Study dates
- 29 Jun 2018to 20 Dec 2019
- Phase
- Phase 4
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged between 18 and 75 years
- ASA Physical status 1 to 3
- Elective or semi-elective supratentorial craniotomy
- Signed informed consent
Who cannot join
- Craniotomy for suprasellar pathologies
- Re-craniotomy at the same site
- Perioperative sodium disorders (Na <130 mEq/L or >150 mEq/L)
- Administration of intravenous mannitol or hypertonic saline 7.5% 24 hours or less before the surgery
- Preoperative obstructive hydrocephalus
- Congestive heart failure
- Renal failure
Trial locations and contacts
2 sites in 1 country.
Greece2 sites
AHEPA University Hospital
Thessaloniki, 56224
Georgia Tsaousi
Thessaloniki, 56346
About this study
Official title: Effect of Isosmotic Doses of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation in Supratentorial Craniotomies
Usage of osmotic agents is a standard practice in neuroanesthesia since cerebral edema is a very common situation for patients with pathology in the brain. Cerebral edema is defined as the accumulation of fluid in the intracellular or extracellular compartments of the brain. Among other situations that have nothing to do with the brain, a supratentorial pathology such as a tumor, traumatic injury or an aneurysm, will lead to disruption of blood-brain barrier, and energy crisis of the cells that will cause mainly vasogenic and cytotoxic cerebral edema. The most common monitoring method for "measuring" cerebral edema is ICP (intracranial pressure) in which normal values are (with differences in the bibliography) 10-15 mmHg.
The osmotic agents used most in neuroanesthesia are mannitol 20% and hypertonic NaCl 7.5% or 3%. Their brain relaxation effectiveness is supposed to be quite the same between the two different agents. Their main difference is that mannitol induces diuresis. Also, electrolyte disorders are another possibility after mannitol infusion. On the other hand, NaCl 7.5% causes vasodilation, does not induce diuresis and hemodynamically, even though it reduces SBP, it raises CO because of its excessive vasodilation. But both reduce cerebral edema due to the change of osmotic pressure in the vessels, that leads to extracting water from brain cells.
Read more
A supratentorial craniotomy is de facto worsening the oxygenation and metabolism condition of the surgical site, adding to the problem the intracranial pathology causes in the first place. So if oxygen provided is low and the metabolic rate is high, the rate of anaerobic metabolism will raise. Measuring the oxygen in the jugular bulb is the most reliable monitoring method of cerebral oxygenation and metabolism.
It becomes evident that optimization of cerebral oxygenation during a craniotomy will possibly affect the outcome of a patient, by improving it. So, if any superiority of one osmotic agent over the other could be demonstrated this will be very helpful in the decision making in routine clinical practice.
Read the detailed description
Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output, temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).
TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.
Protective mechanical ventilation will be chosen (7ml/kg IBW) with a Respiratory rate to obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of choice will be 0.5.
The radial artery catheterization will be applied for direct blood pressure measurement and arterial blood gas sampling ( pH, PaO2, PaCO2, HCO3, BE, Osmolality, Lactic acid, Hb, Glucose, Na, K will be measured).
The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood samples for blood gas analysis. The following oxygenation and metabolic parameters / derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality, Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.
The osmotic agent will be administered 20 minutes before dura matter incision. Before the dura mater opening the subdural space pressure will be measured and relevant CPP will be calculated. Brain Relaxation Score will be assessed by the neurosurgeon.
Phases
- T0: 5 minutes before administration of the osmotic agent
- T15: 15 minutes after administration of the osmotic agent
- T30: 30 minutes after administration of the osmotic agent
- T60: 60 minutes after administration of the osmotic agent
- T90: 90 minutes after administration of the osmotic agent
- T120: 120 minutes after administration of the osmotic agent
- T180: 180 minutes after administration of the osmotic agent
- T240: 240 minutes after administration of the osmotic agent Blood samples for measuring S-100b will be collected at phases T0, T240 and 12 hours after osmotic agent administration.
Postoperative complications, length of ICU stay, GOS-E (Glasgow Outcome Scale) and other neurological deficits will be recorded.
- Being tested
- Mannitol, NaCl 7.5%
- Keywords
- mannitol, hypertonic saline, brain metabolism, brain oxygenation
- Medical subject headings
- Brain Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MannitolDrug
4.6 ml/kg will be administered before dura opening
NaCl 7.5%Drug
2 ml/kg will be administered before dura opening
| Study group | Role | What they receive |
|---|---|---|
| Mannitol 20% | Active comparator | Mannitol 20% (4.6ml/kg) will be administered 20 minutes before dura matter opening. Receives: Drug: Mannitol |
| Hypertonic saline 7.5% | Experimental | Hypertonic saline 7.5% (2ml/kg) will be administered 20 minutes before dura matter opening Receives: Drug: NaCl 7.5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of jugular venous oxygen saturation
Alterations in jugular venous oxygen saturation (%) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Measured: 15 minutes after the end of the infusion of the tested osmotic agent
Secondary outcomes (4)
Changes of S-100b protein
Alterations in S-100b (μg/L) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Measured: 6 hours after the end of the infusion of the tested osmotic agent
Changes in the cardiac index
Alterations in the cardiac index (L/min/m2) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
Measured: 15 minutes after the end of the infusion of the tested osmotic agent
Brain tension after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5% assessed by Brain relaxation Score and subdural pressure
Brain tension graded from 1 to 4 (1 indicates satisfactory brain relaxation and 4 serious brain bulking)
Measured: 2 minutes before dura opening
Functional outcome of participants
Functional status of the participants assessed by Extended GOS ranginging from 1 to 7 (1 indicates death and 7 neurologically intact patient)
Measured: 7 days post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2018
- Study start29 Jun 2018
- Primary completion31 Oct 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain EdemaStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgia Tsaousi, Aristotle University Of Thessaloniki
- Investigators
- Georgia Tsaousi, Principal investigator, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03573999
- Sponsor's protocol ID
- OsmoMetOx
- Status last verified
- Jan 2020
- First submitted
- 20 May 2018
- Last updated
- 7 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Isosmotic Doses of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation in Supratentorial Craniotomies
- ClinicalTrials.gov ID
- NCT03573999
- Acronym / sponsor ID
- OsmoMetOx
- Keywords
- mannitol, hypertonic saline, brain metabolism, brain oxygenation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 29 Jun 2018 (actual)
- Primary completion
- 31 Oct 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 29 Jun 2018 (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.
Usage of osmotic agents is a standard practice in neuroanesthesia since cerebral edema is a very common situation for patients with pathology in the brain. Cerebral edema is defined as the accumulation of fluid in the intracellular or extracellular compartments of the brain. Among other situations that have nothing to do with the brain, a supratentorial pathology such as a tumor, traumatic injury or an aneurysm, will lead to disruption of blood-brain barrier, and energy crisis of the cells that will cause mainly vasogenic and cytotoxic cerebral edema. The most common monitoring method for "measuring" cerebral edema is ICP (intracranial pressure) in which normal values are (with differences in the bibliography) 10-15 mmHg.
The osmotic agents used most in neuroanesthesia are mannitol 20% and hypertonic NaCl 7.5% or 3%. Their brain relaxation effectiveness is supposed to be quite the same between the two different agents. Their main difference is that mannitol induces diuresis. Also, electrolyte disorders are another possibility after mannitol infusion. On the other hand, NaCl 7.5% causes vasodilation, does not induce diuresis and hemodynamically, even though it reduces SBP, it raises CO because of its excessive vasodilation. But both reduce cerebral edema due to the change of osmotic pressure in the vessels, that leads to extracting water from brain cells.
A supratentorial craniotomy is de facto worsening the oxygenation and metabolism condition of the surgical site, adding to the problem the intracranial pathology causes in the first place. So if oxygen provided is low and the metabolic rate is high, the rate of anaerobic metabolism will raise. Measuring the oxygen in the jugular bulb is the most reliable monitoring method of cerebral oxygenation and metabolism.
It becomes evident that optimization of cerebral oxygenation during a craniotomy will possibly affect the outcome of a patient, by improving it. So, if any superiority of one osmotic agent over the other could be demonstrated this will be very helpful in the decision making in routine clinical practice.
Detailed description
Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output, temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).
TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.
Protective mechanical ventilation will be chosen (7ml/kg IBW) with a Respiratory rate to obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of choice will be 0.5.
The radial artery catheterization will be applied for direct blood pressure measurement and arterial blood gas sampling ( pH, PaO2, PaCO2, HCO3, BE, Osmolality, Lactic acid, Hb, Glucose, Na, K will be measured).
The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood samples for blood gas analysis. The following oxygenation and metabolic parameters / derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality, Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.
The osmotic agent will be administered 20 minutes before dura matter incision. Before the dura mater opening the subdural space pressure will be measured and relevant CPP will be calculated. Brain Relaxation Score will be assessed by the neurosurgeon.
Phases
- T0: 5 minutes before administration of the osmotic agent
- T15: 15 minutes after administration of the osmotic agent
- T30: 30 minutes after administration of the osmotic agent
- T60: 60 minutes after administration of the osmotic agent
- T90: 90 minutes after administration of the osmotic agent
- T120: 120 minutes after administration of the osmotic agent
- T180: 180 minutes after administration of the osmotic agent
- T240: 240 minutes after administration of the osmotic agent Blood samples for measuring S-100b will be collected at phases T0, T240 and 12 hours after osmotic agent administration.
Postoperative complications, length of ICU stay, GOS-E (Glasgow Outcome Scale) and other neurological deficits will be recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mannitol 20% | Active comparator | Drug: MannitolMannitol 20% (4.6ml/kg) will be administered 20 minutes before dura matter opening. |
| Hypertonic saline 7.5% | Experimental | Drug: NaCl 7.5%Hypertonic saline 7.5% (2ml/kg) will be administered 20 minutes before dura matter opening |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients aged between 18 and 75 years
- ASA Physical status 1 to 3
- Elective or semi-elective supratentorial craniotomy
- Signed informed consent
Key exclusion criteria (7 listed)
- Craniotomy for suprasellar pathologies
- Re-craniotomy at the same site
- Perioperative sodium disorders (Na <130 mEq/L or >150 mEq/L)
- Administration of intravenous mannitol or hypertonic saline 7.5% 24 hours or less before the surgery
- Preoperative obstructive hydrocephalus
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 |
|---|---|---|
| Mannitol4.6 ml/kg will be administered before dura opening | Drug | Mannitol 20% |
| NaCl 7.5%2 ml/kg will be administered before dura opening | Drug | Hypertonic saline 7.5% |
Primary outcome
Changes of jugular venous oxygen saturation
Time frame: 15 minutes after the end of the infusion of the tested osmotic agent
Alterations in jugular venous oxygen saturation (%) after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5%
4 secondary outcomes
Changes of S-100b protein
Time frame: 6 hours after the end of the infusion of the tested osmotic agent
Changes in the cardiac index
Time frame: 15 minutes after the end of the infusion of the tested osmotic agent
Brain tension after intravenous infusion of isosmotic doses of mannitol 20% and hypertonic saline 7.5% assessed by Brain relaxation Score and subdural pressure
Time frame: 2 minutes before dura opening
Functional outcome of participants
Time frame: 7 days post surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Individual participant dataSharing planned: No
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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.
Georgia Tsaousi principal investigator
Aristotle University Of Thessaloniki
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mannitol and NaCl 7.5% in people with Brain Edema and Metabolic Disturbance, run by Aristotle University Of Thessaloniki at 2 sites in Greece.
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 4 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: finished, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of jugular venous oxygen saturation (time frame: 15 minutes after the end of the infusion of the tested osmotic agent). 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 7 May 2021.