Condition category
Surgery
Date applied
23/08/2010
Date assigned
22/02/2011
Last edited
16/09/2014
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 Neil Morton

ORCID ID

Contact details

Royal Hospital for Sick Children
Dalnair Street
Glasgow
G3 8SJ
United Kingdom

Additional identifiers

EudraCT number

2009-014568-21

ClinicalTrials.gov number

Protocol/serial number

EudraCT number: 2009-014568-21

Study information

Scientific title

A multicentre open study of the performance of an effect-site targeted infusion of propofol used for induction and maintenance of anaesthesia in children under 16 years

Acronym

Study hypothesis

The equilibration of propofol from the plasma compartment to brain can be described using the time to peak effect and keo values for propofol. This is an open study to determine the performance of an effect-site targeted infusion based on the age-dependent values described by Jeleazcov (2008), using the four standard measures of bias, precision, divergence and wobble. These derived parameters estimate quantitatively whether the system over- or under-delivers propofol and how this varies both between patients and for an individual patient over time.

Ethics approval

Not provided at time of registration

Study design

Multicentre open non-randomised non-controlled study

Primary study design

Interventional

Secondary study design

Other

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

General anaesthesia

Intervention

Patients will be recruited from suitable operating lists and after appropriate consent, will undergo induction and maintenance of general anaesthesia using the effect-site targeted infusion of propofol. Patients will have an intravenous (iv) cannula inserted through topically-anaesthetised skin and a bolus of remifentanil 0.5 µg/kg and lignocaine 0.2 mg/kg will be injected to reduce propofol pain at induction. Bispectral index monitoring will be used to monitor depth of anaesthesia throughout the induction and maintenance period.

During the period of maintenance of anaesthesia, the target effect-site concentration will be lowered and a hysteresis loop of depth of anaesthesia against propofol concentration will be populated using the BIS data and plasma samples collected from a second venous cannula. From this, an estimate of the keo value for propofol can be calculated. The period of lightening of anaesthesia may be terminated at any point because of clinical or BIS-derived suspicions of a requirement for greater depth of anaesthesia. The main outcome measure of the performance of the infusion algorithm is calculated from propofol sampling performed during the remainder of the period of anaesthesia using non-linear lixed effects monitoring. A maximum of 5 ml blood will be sampled from each patient.

The involvement of each participant concludes at the time of emergence from anaesthesia.

Intervention type

Drug

Phase

Phase IV

Drug names

Propofol

Primary outcome measures

Performance of an effect-site target controlled infusion (TCI) pharmacokinetic model for children aged 1 to 12 years and weight 6 - 60 kg, as calculated from the four standard parameters described by Varvel et al. The performance error (PE) is calculated from the concentration of propofol measured in whole blood (Cmeas) and the concentration predicted by the software (Cpred) as follows: PE(%) = ((Cmeas-Cpred)/Cpred) x 100. Four standard measures of performance are derived from this value, namely bias, precision, divergence and wobble. These derived parameters estimate quantitatively whether the system over- or under-delivers propofol, and how this varies both between patients and for an individual patient over time.

Secondary outcome measures

1. Population pharmacokinetics of propofol in children aged 1 to 12 years using non-linear effects modelling (NONMEM). This allows the calculation of volume of distribution and clearance of propofol and potential relationships between these pharmacokinetic parameters and the variables of age, gender and weight to be explored.
2. Pharmacodynamic modelling, using bispectral index as a measure of depth of anaesthesia. This will allow direct estimation of the blood-brain equilibration rate-constant (keo) for propofol in this patient population.
3. Establish a safety profile for effect-site TCI propofol based on the pharmacodynamics of Jeleazcov et al by identifying the rate of adverse events associated with the use of effect-site targeted propofol infusion

Overall trial start date

01/12/2010

Overall trial end date

30/11/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. American Society of Anaesthesiologists (ASA) grade 1 and 2 healthy male and female children aged 1 to 12 years (inclusive)
2. Weight 6 - 60 kg
3. Elective surgery requiring general anaesthesia
4. Surgery or procedure of expected duration of at least 30 minutes
5. Written parental consent or child's consent if competent, for inclusion
6. Child appropriate for intravenous induction and maintenance of anaesthesia with propofol
7. Agreement to undergo intravenous induction of anaesthesia
8. No contraindication to application of topical local anaesthesia prior to cannulation

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

50

Participant exclusion criteria

1. Parental refusal or refusal of child if competent
2. Allergy to propofol or any constituent of propofol
3. Sensitivity to adhesive agents, as used in the Bispectral Index (BIS) measurement strip
4. Refusal of intravenous induction
5. Need for sedative premedication
6. Inadequate topical analgesia for intravenous cannulation
7. Inability to site intravenous cannula within two attempts

Recruitment start date

01/12/2010

Recruitment end date

30/11/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Hospital for Sick Children
Glasgow
G3 8SJ
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde (UK)

Sponsor details

Recearch and Development Central Office
Western Infirmary
Glasgow
G11 6NT
United Kingdom

Sponsor type

Government

Website

http://www.nhsggc.org.uk/content/

Funders

Funder type

Research organisation

Funder name

National Institute of Academic Anaesthesia (NIAA) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Yorkhill Children's Foundation (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes