Validation Study of Covariates Model (VaSCoM) for Propofol

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Golden Jubilee National Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Golden Jubilee National Hospital
ClinicalTrials.gov Identifier:
NCT01492712
First received: December 8, 2011
Last updated: December 15, 2011
Last verified: December 2011
  Purpose

Anaesthesia for surgical procedures can be provided using a continuous infusion of intravenous drug. The most commonly used drug for this technique is propofol. Infusion devices programmed with pharmacokinetic models can be used to infuse propofol to achieve a target blood concentration. These pharmacokinetic models predict the rate of distribution of propofol within the body and also the rate at which it is cleared. In practice, the anaesthetist enters patient details such as age, sex and weight as well as a target blood concentration of propofol. The infusion device then infuses propofol at the appropriate rate to achieve this concentration.

White and colleagues recently published the Covariates Model for propofol. It is anticipated that this model will have reduced bias and inaccuracy compared to the models in current clinical use. The VaSCoM study has three objectives:

  1. Prospective validation of the Covariates Model
  2. Modelling of the effect site concentration of propofol
  3. Comparison of propofol concentration in venous and arterial blood samples

To achieve the above objectives, patients over 18 years of age and undergoing elective non-cardiac surgery will be recruited to the study. Anaesthesia will be delivered using a target controlled infusion device programmed with the Covariates Model for propofol. The target blood concentrations will be set according to a pre-determined schedule and all measurements will be made prior to the start of surgery.

Prospective validation of the Covariates Model will be done by comparing blood concentration of propofol predicted by the model to those actually measured. These results will then be compared to the predictions made using the models in current clinical practice.

Modelling of the effect site means predicting the concentration of propofol in the brain for a given blood concentration. This will involve using depth of anaesthesia monitors (such as bispectral index) as surrogate markers of brain concentration and comparing this to the predicted and measured blood concentrations of propofol.

Finally, important information on the distribution and clearance of propofol can be gained through the comparison of venous and arterial blood samples. In this study, simultaneous sampling of venous and arterial blood will facilitate this comparison.


Condition Intervention
Target Controlled Infusion of Propofol
Drug: Propofol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Official Title: Validation Study of Covariates Model (VaSCoM) for Propofol

Resource links provided by NLM:


Further study details as provided by Golden Jubilee National Hospital:

Primary Outcome Measures:
  • Performance error of predicted blood propofol concentration (venous blood samples) [ Time Frame: 1.5, 5, 16.5, 20, 31.5, 35, 45-60 minutes post infusion start time ] [ Designated as safety issue: Yes ]

    Performance error is calculated as:

    ((Measured blood concentration - Predicted blood concentration)/ Predicted blood concentration) x 100

    The median performance error and the absolute performance error can then be calculated as measures of bias and inaccuracy respectively.



Secondary Outcome Measures:
  • Depth of anaesthesia [ Time Frame: 0 to 45-60 minutes post infusion start time ] [ Designated as safety issue: No ]
    Depth of anaesthesia (as measured by bispectral index and index of consciousness) will be used as a surrogate marker of propofol effect site concentration. By using complex statistical analysis to compare depth of anaesthesia to measured and predicted blood concentrations, we aim to determine the Keo. This is the rate constant for elimination of propofol from the effect site compartment and will be incorporated to the Covariates Model to predict brain concentration for a given blood concentration of propofol.

  • Comparison of performance errors calculated from venous blood samples to performance errors calculated from arterial blood samples [ Time Frame: 1.5, 5, 16.5, 20, 31.5, 35, 45-60 minutes post infusion start time ] [ Designated as safety issue: No ]

    Performance error is calculated as:

    ((Measured blood concentration - Predicted blood concentration)/ Predicted blood concentration) x 100



Estimated Enrollment: 30
Study Start Date: January 2011
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low-high-low blood target concentration
Patients in the low-high-low group will receive an infusion of propofol with an initial blood target concentration of 2 mcg/ml. After 15 minutes the target will be increased to 5 mcg/ml and after a further 15 minutes the target will be reduced back to 2 mcg/ml for a further 15 to 30 minutes.
Drug: Propofol
Patients in the low-high-low group will receive an infusion of propofol with an initial blood target concentration of 2 mcg/ml. After 15 minutes the target will be increased to 5 mcg/ml and after a further 15 minutes the target will be reduced back to 2 mcg/ml for a further 15 to 30 minutes.
Experimental: High-low-high target blood concentration
Patients in the high-low-high group will receive an infusion of propofol with an initial blood target concentration of 5 mcg/ml. After 15 minutes the target will be reduced to 2 mcg/ml and after a further 15 minutes the target will be increased back to 5 mcg/ml for a further 15 to 30 minutes.
Drug: Propofol
Patients in the high-low-high group will receive an infusion of propofol with an initial blood target concentration of 5 mcg/ml. After 15 minutes the target will be reduced to 2 mcg/ml and after a further 15 minutes the target will be increased back to 5 mcg/ml for a further 15 to 30 minutes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged over 18 years
  • ASA I/II
  • Elective non-cardiac surgery expected to last longer than 30 minutes

Exclusion Criteria:

  • Patient refusal or unable to consent
  • Premedication, sedative or anaesthetic in the previous 12 hours
  • Pre-operative GCS less than 15
  • ASA III/IV
  • Allergy to constituents of propofol
  • Excess alcohol intake
  • Drug abuse
  • Mental retardation
  • Difficult airway
  • BMI over 35
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01492712

Contacts
Contact: Stefan Schraag 00441419515609 stefanschraag@btinternet.com

Locations
United Kingdom
Golden Jubilee National Hospital Recruiting
Clydebank, United Kingdom, G81 4HX
Contact: Stefan Schraag    00441419515609    stefanschraag@btinternet.com   
Principal Investigator: Stefan Schraag         
Sponsors and Collaborators
Golden Jubilee National Hospital
Investigators
Principal Investigator: Stefan Schraag Golden Jubilee National Hospital
  More Information

No publications provided

Responsible Party: Golden Jubilee National Hospital
ClinicalTrials.gov Identifier: NCT01492712     History of Changes
Other Study ID Numbers: VaSCoM005, 2009-017900-10
Study First Received: December 8, 2011
Last Updated: December 15, 2011
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Golden Jubilee National Hospital:
Propofol
Pharmacokinetics
Pharmacodynamics
Infusion Pumps

Additional relevant MeSH terms:
Propofol
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014