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RecruitingNCT06417645Eleved PDUpdated May 16, 2024

Re-evaluation of the Effect Site Model of the PKPD Propofol Eleveld Model

A Phase 4 interventional study of fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio) in Healthy and Surgery, sponsored by Universidad del Desarrollo. Recruiting at 1 site in Chile. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-05-16.

Sponsored by Universidad del Desarrollo · Phase 4, Interventional, and Diagnostic

Phase
Phase 4
Study type
Interventional
Enrollment
24
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

in healthy patients undergoing elective surgery, after a very slow induction, using Eleveld's kinetics as a reference, after loss of consciousness (LOC) and intubation, proceed to infuse propofol until 1% burst suppression ratio is obtained. Then return to the LOC concentration. The BISindex predicted by the model and the real one will be evaluated. The evolution of spectral density frequencies over time will also be evaluated.

Read the detailed description

Eleveld is a recently developed PKPD model of propofol, which includes multiple covariates in its pharmacokinetics.

This model, called Universal, includes data from all studies conducted with plasma levels in the world, where the principal investigator (PSV) has been directly involved.

For pharmacodynamics (PD), Eleveld, includes processed electroencephalogram (EEG) readings, but only by nominal BIS index.

The use of BIS as a unique marker of propofol hypnosis shows multiple limitations as it results from a computer algorithmic application, which can be influenced by drugs, inter-individual variability, among others.

Therefore, to determine the effect there are nowadays more accurate tools such as spectrogram processing and determination of alpha power by spectral density (PDS).

This project aims to re-evaluate the modelling of the temporal behaviour of the effect in the BIS index, using the reference of the Eleveld kinetic model, associated to a spectrogram that allows the evaluation of the alpha and delta band dynamics as a predictor of the propofol effect.

In our study we intend to replace the BIS value by the alpha and delta power progress in decibels (dB) and eventually build a pharmacodynamic (PD) model with a marker more associated to the specific cortical electrical phenomenon.

02

Conditions studied

  • Healthy
  • Surgery

Keywords

  • propofol, Eleveld, BIS, predicted effect site model, non-lineal behavior
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • ASA I-II patients between 18 and 60 years of age, who undergo elective surgery in the central ward of the Hospital Base San José Osorno, Chile. Consecutive patients from the beginning of the study up to 12 months from the admission of the first patient.

Exclusion criteria

Exclusion Criteria:

  • Emergency surgery patient.
  • Patients with dementia, delirium or altered state of consciousness.
  • Full stomach or risk of aspiration.
  • Allergic to propofol.
04

Study design

Phase
Phase 4
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
24 participants (estimated)

Study arms

  • Experimental
    BIS predicted vs real

    After slow propofol induction and standard monitoring with BIS EEG monitor. The propofol infusion guided by iTIVA simulator (Android / iOS) using Eleveld kinetic model. LOC (defined as loss of response to loud call and shoulder movement-touch), the same concentration of propofol will be maintained for 5 minutes to assess EEG stability. .Intubation will proceed as usual, starting remifentanil at 4.5 ng/ml and rocuronium bromide 0.6 mg/kg. After 5 min and before the start of surgery, propofol will be infused at 15 mg/kg/h until 1% BSR is reached, observed on the BIS monitor, and then return to the rate that represents the LOC concentration. EEG data shall be retrieved from the BIS monitor via USB. Post hoc using the software tivatrainer.com we will simulate the Eleved calculated plasma concentration and the Bis prediction with our BIS real data.

    Drug: fixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)

Interventions

  • Drugfixed propofol infusion 15 mg/kg/h until 1% BSR (burst suppression ratio)

    after a slow induction with propofol to loss of consiousness (LOC), we proceed to give remifentanil TCI and rocuronium and intubate the patient. After 5 min we infuse 15 mg/kg/h until 1%BSR observe in the BIS monitor. Then we reduce the TCI LOC predicted concentration.

05

What researchers measure

Primary outcomes

  1. predicted BIS index vs real BIS index

    we compare the BIS predicted from the Eleveld model vs the response of our patients uring all the anesthesia procedure

    Time frame: anesthesia

Secondary outcomes

  1. evaluation of the evolution of the EEG frequency bands

    Evaluate the differents EEG frequency bands at LOC, at maximal perturbation and when we reach again the LOC predicted concentration

    Time frame: anesthesia

06

Study locations

1 of 1 sites recruiting
  • Hospital Base san José de Osorno
    Osorno, Chile
    Recruiting
07

References and documents

Publications

  • Sepulveda PO, Mora X. [Reevaluation of the time course of the effect of propofol described with the Schnider pharmacokinetic model]. Rev Esp Anestesiol Reanim. 2012 Dec;59(10):542-8. doi: 10.1016/j.redar.2012.07.019. Epub 2012 Oct 4. Spanish. PubMed 23040653 ↗
  • Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12. Erratum In: Br J Anaesth. 2018 Aug;121(2):519. doi: 10.1016/j.bja.2018.05.045. PubMed 29661412 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06417645
Lead sponsor
Universidad del Desarrollo
Collaborators
Technical University of Munich
Responsible party
Pablo O. Sepulveda (Dr. Med, Universidad del Desarrollo) — Principal investigator
First posted
May 16, 2024
Start date
Sep 1, 2013
Primary completion
Sep 15, 2023
Completion
Sep 15, 2024 (estimated)
Last update
May 16, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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