Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
USA30217
Study information
Scientific title
Acronym
Study hypothesis
To compare the safety and efficacy of analgesia-based sedation with conventional hypnotic-based sedation in patients with brain injuries requiring sedation during mechanical ventilation.
Ethics approval
Not provided at time of registration.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Neurotrauma
Intervention
The study was designed to compare the safety and efficacy of analgesia-based sedation, using remifentanil, with conventional hypnotic-based sedation in patients with brain injuries requiring sedation during mechanical ventilation. Patients were randomised on a 2:1:1 basis to receive either an analgesia-based treatment regimen or a hypnotic-based treatment regimen:
1. Analgesia-based treatment regimen (n = 84): remifentanil was initiated and titrated to provide optimal sedation and analgesia before the addition of a hypnotic agent, according to a predefined dosing algorithm
2. Hypnotic-based treatment regimen: patients received the opioid fentanyl (n = 37) or morphine (n = 40) and a hypnotic agent for analgesia and sedation which were administered simultaneously and then titrated to response
For all three treatment groups, on days 1 - 3 the hypnotic agent was propofol, on days 4 - 5 propofol was substituted with midazolam.
Patient monitoring:
All patients were intensively monitored throughout the study. Baseline Glasgow Coma Score (GCS), SAS, Pain intensity (PI), mean arterial pressure (MAP) and heart rate (HR) were recorded prior to the administration of study drugs. When available, intra-cranial pressure (ICP) and cerebral perfusion pressure (CPP) were also recorded. SAS, PI, MAP, HR, ICP and CPP were then recorded at the time of any changes in study drug infusion rates or bolus dosing and at 10 minute intervals afterwards until adequate SAS/PI scores were attained. Once target SAS and PI scores were attained, haemodynamic monitoring was performed at 1 - 4 hour intervals. In addition, haemodynamic parameters were recorded at the start of down-titrations of study drugs for neurological assessment of patients and when the assessments were completed. The SAS, PI, MAP, HR, ICP and CPP were also recorded at the start of and at the time of adequate transitioning from propofol to midazolam at the end of day 3 and if a patient was extubated before day 5 of the study treatment period. These parameters were also recorded at the start of the final transition to an alternative analgesia/sedation regimen at the end of study day 5, at 20 min intervals after each down-titration of the remifentanil infusion as part of this process, at 30 and 60 min after the termination of the infusion and at final transition to an alternative opioid.
Patients were continuously assessed for the occurrence of adverse events until 24 hours after permanent discontinuation of the study drugs or until ICU discharge if this occurred earlier. Serious adverse events were defined as adverse events that resulted in any of the following outcomes: death, life-threatening event, prolongation of hospitalisation, a disability/incapacity. Important medical events which did not result in death or were not life-threatening, were considered serious adverse events when, based upon appropriate medical judgement, they jeopardised the patient and required medical or surgical intervention to prevent one of the outcomes listed above.
Intervention type
Drug
Phase
Not Specified
Drug names
Remifentanil, fentanyl
Primary outcome measure
Not provided at time of registration.
Secondary outcome measures
Not provided at time of registration.
Overall trial start date
01/01/2004
Overall trial end date
31/12/2004
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Acute, severe neurological insult/injury
2. Elective or emergency neurosurgery
3. Aged 18 - 80 years
4. Weighed less than or equal to 120 kg
5. Admitted into the ICU within the past 24 hours, were intubated and were expected to require mechanical ventilation for 1 - 5 days
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
161
Participant exclusion criteria
1. Had or were likely to require:
1.1. Long-acting (or continuous administration of) neuromuscular blocking drugs to facilitate mechanical ventilation during the study period
1.2. Barbiturate administration prior to or during the study period
1.3. Epidural block during the maintenance or extubation phases of the study
2. Failed to demonstrate signs of recovery/responsiveness within 6 hours of stopping any analgesia/sedation regimen in use at the time of screening for study entry
3. Likely to require a tracheostomy with spontaneous ventilation within five days of starting study drug treatment
4. Suffered severe, associated traumatic injury, had a neurological condition that might affect the ability to assess their Sedation-Agitation Scale (SAS) score, were admitted for status epilepticus, had moderate or severe renal impairment (predicted creatinine clearance of less than 50 ml/min)
5. History of allergy to opioids, benzodiazepines, propofol or of alcohol/drug abuse
6. Pregnant or lactating women
Recruitment start date
01/01/2004
Recruitment end date
31/12/2004
Locations
Countries of recruitment
Austria, Belgium, Germany, Greece, Netherlands, Spain
Trial participating centre
Intensive Care Unit
Athens
Greece
Funders
Funder type
Industry
Funder name
GlaxoSmithKline (UK)
Alternative name(s)
GlaxoSmithKline plc., GSK
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results in http://www.ncbi.nlm.nih.gov/pubmed/15312228
Publication citations
-
Results
Karabinis A, Mandragos K, Stergiopoulos S, Komnos A, Soukup J, Speelberg B, Kirkham AJ, Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]., Crit Care, 2004, 8, 4, R268-80, doi: 10.1186/cc2896.