Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents

Traumatic Brain Injury Clinical Trial

— THIC Cu  

Official title:

Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents. A Controlled Randomized Study Versus Placebo

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02404779
• Other study ID #: CHU-0225
• Secondary ID: 2014-004951-30
• Status: Recruiting
• Phase: Phase 4
• Start date: March 19, 2015
• Est. completion date: June 18, 2022

Study information

• Verified date: June 2020
• Source: University Hospital, Clermont-Ferrand
• Contact: Patrick LACARIN
• Phone: 04 73 75 11 95
• Email: placarin[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Severely brain injured patients are at high risk of intracranial hypertension. Among medical treatments (sedatives), neuromuscular blocking agents (NMBA) are recommended by french but not english speaking societies.

Effects of NMBA are unknown. The present study is designed to compare the effects of NMBA versus placebo in the treatment of intracranial hypertension, and the underlying physiopathologic effects.

Description:

In case of intracranial hypertension, french neurocritical care society argue for the use of neuromuscular blocking agents before osmotherapy, barbituric coma, hypothermia and craniectomy.

English speaking societies don't sustain this approach. Since then, the use of NMBA remains controversial in case of intracranial hypertension and no study is available.

We propose to study severely brain injured patients presenting with intracranial hypertension and treat them with cisatracurium besilate or placebo.

Our hypothesis is that neuromuscular blockade might act on several parameters:

• Hemodynamics

• respiratory parameters, mechanical ventilation and blood gaz analysis

• cerebral velocities

• diminished O2 peripheral consumption

• cerebrospinal diffusion and concentration of cisatracurium and a metabolite laudanosine We wish to assess changes in ICP according to the above parameters in a controlled randomized non blinded fashion against placebo (NaCl 0,9%).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: June 18, 2022
• Est. primary completion date: March 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• - Age over 18

• Mechanical ventilation and deep sedation

• Severe traumatic brain injury

• Intracranial hypertension (ICP > 20 mmHg during > 15 minutes)

• Intracranial pressure monitoring

• Hemodynamically stable

Exclusion Criteria:

• - History of anaphylaxia with neuromuscular agents

• Hemodynamic instability

• Pregnant and/or breast feeding women

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Hypertension
• Intracranial Hypertension
• Traumatic Brain Injury

Intervention

Drug:
• cisatracurium besilate

Other:
• Placebo

Locations

Country	Name	City	State
France	CHU de Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	area under the curve of the temporal evolution of intracranial pressure	The primary outcome is the area under the curve of the temporal evolution of intracranial pressure, over a period of 30 minutes after the administration of neuromuscular blocking agent or placebo.	at day 1
Secondary	Course of intracranial and cerebral perfusion pressures and various cerebral monitoring data if available (SvjO2, PtiO2)		at day 1
Secondary	Monitoring of the time spent by intracranial pressure above 20 mmHg using continuous recording		at day 1
Secondary	Course of intracranial pressure based on the type of brain injury	diffuse axonal injury, subarachnoid hemorrhage, intracerebral hematoma)	at day 1
Secondary	Monitoring of the curare effect	train of four and PTC	at day 1
Secondary	Course of ventilation parameters	tidal volume, FiO2, PEEP	at day 1
Secondary	Course of transcranial Doppler data	velocities	at day 1
Secondary	Course of arterial blood gas data	pH, paO2, paCO2, Excess Base, HCO3-	at day 1
Secondary	Course of plasma and cerebrospinal fluid concentrations of cistracurium and laudanosine		at day 1
Secondary	Cerebrospinal fluid concentrations of cisatracurium and laudanosin in case of cerebrospinal fluid derivation		at day 1
Secondary	Occurrence of cardiovascular complications	hypotension, myocardial ischemia	at day 1
Secondary	Occurrence of pulmonary complications	acute respiratory distress syndrome, pneumonia acquired under mechanical ventilation	at day 1
Secondary	Occurrence of renal complications	use of renal replacement therapy	at day 1
Secondary	Occurrence of infectious complications		at day 1
Secondary	Doses of vasopressors or catecholamines		at day 1
Secondary	Need to increase therapeutics	barbiturate coma, hypothermia, osmotherapy, decompressive craniectomy	at day 1