Condition category
Injury, Occupational Diseases, Poisoning
Date applied
24/05/2004
Date assigned
25/05/2004
Last edited
08/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Andreas Karabinis

ORCID ID

Contact details

Intensive Care Unit
Genimatas General Hospital
Athens
Greece

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 measures

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

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

Sponsor information

Organisation

GlaxoSmithKline (UK)

Sponsor details

Greenford Road
Greenford
UB6 OHE
United Kingdom

Sponsor type

Industry

Website

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

Results - basic reporting

Publication summary

Results in http://www.ncbi.nlm.nih.gov/pubmed/15312228

Publication citations

  1. 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.

Additional files

Editorial Notes