Traumatic Brain InjuryPhase 3NCT01028339
Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values
A Phase 3 study testing Hypertonic saline and Mannitol in people with Traumatic Brain Injury, run by Direction Centrale du Service de Santé des Armées at 1 site in France.
Trial summary
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the same effects on PtiO2 and cerebral metabolism studied through microdialysis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Hypertonic saline and Mannitol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2008to Dec 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe Traumatic brain injury monitored with ICP, PtiO2 and cerebral microdialysis
- And ICP> 20 mm Hg needing osmotherapy
- And approval of the next of kind
Who cannot join
- Bilateral fixed dilated pupils
- Contra-indication to multimodal neuromonitoring
- Previous CNS disease
- Contra-indication to HS (cardiac insufficiency,...)
- Natremia > 155 mmol/L or osmolarity > 320 mOsm/L
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mannitol Versus Hypertonic Saline to Treat Intracranial Hypertension After Severe Traumatic Brain Injury : a Comparative Study on the Effects on PtiO2 and Microdialysis Values
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the same effects on PtiO2 and cerebral metabolism studied through microdialysis.
Read the detailed description
Mannitol is frequently used to treat intracranial hypertension after TBI. However, it can be deleterious, particularly through hyperdiuresis and risks of hypovolemia. It also needs volume compensation and induces logistical problem because of needs of high infused volume to achieve osmolar load and avoid hypotension. Finally, some recent studies tend to prove superiority of hypertonic saline versus mannitol on the prognosis of TBI. especially through modulation of inflammatory reactions mechanisms and apoptosis.
We would like to prove non inferiority of hypertonic saline versus mannitol after TBI to allow its large utilization, especially by field military doctors with specific logistical problems. For that, more than the single Intracranial Pressure, we want to study effects of HS vs mannitol not only on PtiO2 but also on cerebral microdialysis which gives informations on focal metabolism with profiles of ischemia, metabolic crisis, hyperglycolysis (possible reflect of neuronal restoration) and normality.
- Conditions
- Traumatic Brain Injury
- Being tested
- Hypertonic saline, Mannitol
- Keywords
- traumatic brain injury, PtiO2, Cerebral microdialysis, Osmotherapy, hypertonic saline, mannitol
- 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.
Hypertonic salineDrug
2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch
MannitolDrug
Mannitol
| Study group | Role | What they receive |
|---|---|---|
| Mannitol | Active comparator | Not described Receives: Drug: Mannitol |
| Hypertonic saline | Experimental | Not described Receives: Drug: Hypertonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of HS versus mannitol on lactate/pyruvate ratio
Measured: 20 min, 40 min, H1, H2, H3 and H4
Secondary outcomes (8)
Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose
Measured: 20 min, 40 min, H1, H2, H3 and H4
Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy
Measured: 20 min, 40 min, H1, H2, H3 et H4
Duration of ICP<20 mm Hg after osmotherapy
Measured: 20 min, 40 min, H1, H2, H3 and H4
Interstitial osmolarity
Measured: 20 min, 40 min and H1
Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma
Measured: Day after osmotherapy
Length of stay
Measured: After leaving the unit
Mortality
Measured: 28th days
Glasgow outcome scale
Measured: 6th month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startJul 2008
- Primary completionJun 2012
- Study completionDec 2012 (estimated)
Why it stopped: No patients enrolled during 2 years
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Direction Centrale du Service de Santé des Armées
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, BORET Henry, Direction Centrale du Service de Santé des Armées
- Investigators
- Henry BORET, MD, Principal investigator, Direction Centrale du Service de Santé des Armées
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01028339
- Sponsor's protocol ID
- SSH versus mannitol
- Status last verified
- Aug 2012
- First submitted
- 3 Dec 2009
- Last updated
- 8 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, Martin C. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. 2003 Jun;31(6):1683-7. doi: 10.1097/01.CCM.0000063268.91710.DF.
PubMed 12794404Sakowitz OW, Stover JF, Sarrafzadeh AS, Unterberg AW, Kiening KL. Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma. 2007 Feb;62(2):292-8. doi: 10.1097/01.ta.0000203560.03937.2d.
PubMed 17297315Soustiel JF, Vlodavsky E, Zaaroor M. Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury. Brain Res. 2006 Jul 26;1101(1):136-44. doi: 10.1016/j.brainres.2006.05.045. Epub 2006 Jun 19.
PubMed 16787640
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mannitol Versus Hypertonic Saline to Treat Intracranial Hypertension After Severe Traumatic Brain Injury : a Comparative Study on the Effects on PtiO2 and Microdialysis Values
- ClinicalTrials.gov ID
- NCT01028339
- Acronym / sponsor ID
- SSH versus mannitol
- Conditions
- Traumatic Brain Injury
- Keywords
- traumatic brain injury, PtiO2, Cerebral microdialysis, Osmotherapy, hypertonic saline, mannitol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No patients enrolled during 2 years
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Direction Centrale du Service de Santé des ArméesUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Dec 2012 (estimated)
- First posted
- 9 Dec 2009 (estimated)
- 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.
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the same effects on PtiO2 and cerebral metabolism studied through microdialysis.
Detailed description
Mannitol is frequently used to treat intracranial hypertension after TBI. However, it can be deleterious, particularly through hyperdiuresis and risks of hypovolemia. It also needs volume compensation and induces logistical problem because of needs of high infused volume to achieve osmolar load and avoid hypotension. Finally, some recent studies tend to prove superiority of hypertonic saline versus mannitol on the prognosis of TBI. especially through modulation of inflammatory reactions mechanisms and apoptosis.
We would like to prove non inferiority of hypertonic saline versus mannitol after TBI to allow its large utilization, especially by field military doctors with specific logistical problems. For that, more than the single Intracranial Pressure, we want to study effects of HS vs mannitol not only on PtiO2 but also on cerebral microdialysis which gives informations on focal metabolism with profiles of ischemia, metabolic crisis, hyperglycolysis (possible reflect of neuronal restoration) and normality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mannitol | Active comparator | Drug: Mannitol |
| Hypertonic saline | Experimental | Drug: Hypertonic saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Severe Traumatic brain injury monitored with ICP, PtiO2 and cerebral microdialysis
- And ICP> 20 mm Hg needing osmotherapy
- And approval of the next of kind
Key exclusion criteria (5 listed)
- Bilateral fixed dilated pupils
- Contra-indication to multimodal neuromonitoring
- Previous CNS disease
- Contra-indication to HS (cardiac insufficiency,...)
- Natremia > 155 mmol/L or osmolarity > 320 mOsm/L
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 |
|---|---|---|
| Hypertonic saline2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch | Drug | Hypertonic saline |
| MannitolMannitol | Drug | Mannitol |
Primary outcome
Effects of HS versus mannitol on lactate/pyruvate ratio
Time frame: 20 min, 40 min, H1, H2, H3 and H4
8 secondary outcomes
Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose
Time frame: 20 min, 40 min, H1, H2, H3 and H4
Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy
Time frame: 20 min, 40 min, H1, H2, H3 et H4
Duration of ICP<20 mm Hg after osmotherapy
Time frame: 20 min, 40 min, H1, H2, H3 and H4
Interstitial osmolarity
Time frame: 20 min, 40 min and H1
Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma
Time frame: Day after osmotherapy
Length of stay
Time frame: After leaving the unit
Mortality
Time frame: 28th days
Glasgow outcome scale
Time frame: 6th month
Results and safety
The study was stopped early (reason given: No patients enrolled during 2 years). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2012.
- Background: PubMed 12794404Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, Martin C. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. 2003 Jun;31(6):1683-7. doi: 10.1097/01.CCM.0000063268.91710.DF.
- Background: PubMed 17297315Sakowitz OW, Stover JF, Sarrafzadeh AS, Unterberg AW, Kiening KL. Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma. 2007 Feb;62(2):292-8. doi: 10.1097/01.ta.0000203560.03937.2d.
- Background: PubMed 16787640Soustiel JF, Vlodavsky E, Zaaroor M. Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury. Brain Res. 2006 Jul 26;1101(1):136-44. doi: 10.1016/j.brainres.2006.05.045. Epub 2006 Jun 19.
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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.
Henry BORET, MD principal investigator
Direction Centrale du Service de Santé des Armées
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hypertonic saline and Mannitol in people with Traumatic Brain Injury, run by Direction Centrale du Service de Santé des Armées at 1 site in France.
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 5 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: stopped early, as of the sponsor's last update on 8 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 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?
The study was stopped early (reason given: No patients enrolled during 2 years). Results are not available in the source record.
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?
Effects of HS versus mannitol on lactate/pyruvate ratio (time frame: 20 min, 40 min, H1, H2, H3 and H4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01028339, which also lists 3 linked publications.
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 8 Aug 2012.