Validation Study of Covariates Model (VaSCoM) for Propofol

NCT ID: NCT01492712

Last Updated: 2017-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-02-28

Brief Summary

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.

Conditions

Target Controlled Infusion of Propofol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Propofol

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Propofol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Golden Jubilee National Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Schraag

Role: PRINCIPAL_INVESTIGATOR

Golden Jubilee National Hospital

Locations

Golden Jubilee National Hospital

Clydebank, , United Kingdom

Countries

United Kingdom

References

Hawthorne C, Shaw M, Campbell R, Sutcliffe N, McKelvie S, Schraag S. Clinical Validation of the Covariates Pharmacokinetic Model for Propofol in an Adult Population. Drugs R D. 2022 Dec;22(4):289-300. doi: 10.1007/s40268-022-00404-4. Epub 2022 Oct 7.

Reference Type: DERIVED

PMID: 36207643 (View on PubMed)

Other Identifiers

2009-017900-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VaSCoM005

Identifier Type: -

Identifier Source: org_study_id