Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values

Traumatic Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01028339
• Other study ID #: SSH versus mannitol
• Status: Terminated
• Phase: Phase 3
• First received: December 3, 2009
• Last updated: August 7, 2012
• Start date: July 2008
• Est. completion date: December 2012

Study information

• Verified date: August 2012
• Source: Direction Centrale du Service de Santé des Armées
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Intracranial Hypertension
• Traumatic Brain Injury

Intervention

Drug:
• Hypertonic saline
2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch
• Mannitol
Mannitol

Locations

Country	Name	City	State
France	HIA Sainte Anne	Toulon

Sponsors (1)

Lead Sponsor	Collaborator
Direction Centrale du Service de Santé des Armées

Country where clinical trial is conducted

France, 

References & Publications (3)

Sakowitz 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. — View Citation

Soustiel 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. Epub 2006 Jun 19. — View Citation

Vialet R, Albanèse 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of HS versus mannitol on lactate/pyruvate ratio		20 min, 40 min, H1, H2, H3 and H4	No
Secondary	Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose		20 min, 40 min, H1, H2, H3 and H4	No
Secondary	Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy		20 min, 40 min, H1, H2, H3 et H4	No
Secondary	Duration of ICP<20 mm Hg after osmotherapy		20 min, 40 min, H1, H2, H3 and H4	No
Secondary	Interstitial osmolarity		20 min, 40 min and H1	No
Secondary	Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma		Day after osmotherapy	No
Secondary	Length of stay		After leaving the unit	No
Secondary	Mortality		28th days	No
Secondary	Glasgow outcome scale		6th month	No