Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents (THIC Cu)

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

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.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury; Intracranial Hypertension
• Intervention / Treatment: Other: Placebo; Drug: cisatracurium besilate

Detailed 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%).

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU de Clermont-Ferrand
    • Principal Investigator: Sophie KAUFFMANN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CISATRACURIUM; To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.	Drug: cisatracurium besilate
Placebo Comparator: PLACEBO; To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2015
• Primary Completion (Anticipated): March 19, 2022
• Study Completion (Anticipated): June 18, 2022

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 31, 2015
• First Posted (Estimate): April 1, 2015

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: ICU; Traumatic brain injury; Mechanical ventilation; Deep sedation; Intracranial hypertension; Cisatracurium; Neuromuscular Blocking Agent; Randomization versus placebo
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Hypertension; Brain Injuries; Brain Injuries, Traumatic; Intracranial Hypertension; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Blocking Agents; Cisatracurium
• Other Study ID Numbers: CHU-0225; 2014-004951-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No