## Protocol Section
### Identification Module
**NCT ID:** NCT06417645

**Acronym:** Eleved PD

**Brief Title:** Re-evaluation of the Effect Site Model of the PKPD Propofol Eleveld Model

**Official Title:** the BIS Index Response is Poorly Described by Propofol Effect Site Eleveld's Model After Applying a Perturbation

#### Organization Study ID Info
**ID:** CEC-SSLR ord: 459
#### Organization
**Class:** OTHER
**Full Name:** Universidad del Desarrollo
### Status Module
#### Completion Date
**Date:** 2024-09-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-11

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2023-09-15

**Type:** ACTUAL

#### Start Date
**Date:** 2013-09-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-11
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Technical University of Munich

#### Lead Sponsor

**Class:** OTHER

**Name:** Universidad del Desarrollo

#### Responsible Party

**Investigator Affiliation:** Universidad del Desarrollo

**Investigator Full Name:** Pablo O. Sepulveda

**Investigator Title:** Dr. Med

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief 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.

**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.

### Conditions Module

**Conditions:**

- Healthy

- Surgery

**Keywords:**

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

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** healthy patients proposed for elective surgery longer than 60 min, received a standard protocol TCI iv anesthesia with EEG BIS index monitoring

##### Masking Info

**Masking:** NONE

**Primary Purpose:** DIAGNOSTIC

#### Enrollment Info

**Count:** 24

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

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

**Label:** BIS predicted vs real

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- BIS predicted vs real

**Description:** 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.

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

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** predicted BIS index vs real BIS index

**Time Frame:** anesthesia

#### Secondary Outcomes

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

**Measure:** evaluation of the evolution of the EEG frequency bands

**Time Frame:** anesthesia

### Eligibility Module

**Eligibility Criteria:** 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:

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

**Healthy Volunteers:** True

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Osorno

**Contacts:**

***Contact 1:***

- **Email:** pasevou@gmail.com

- **Name:** Pablo O Sepulveda, Dr. Med

- **Phone:** 056994793336

- **Role:** CONTACT

***Contact 2:***

- **Email:** ignaciobarrac@icloud.com

- **Name:** Ignacio Barra, Dr. Med

- **Phone:** 056951883419

- **Role:** CONTACT

**Country:** Chile

**Facility:** Hospital Base san José de Osorno

**Status:** RECRUITING

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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.

**PMID:** 23040653

**Citation:** 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.

**PMID:** 29661412

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000006993

- Term: Hypnotics and Sedatives

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018686

- Term: Anesthetics, Intravenous

- ID: D000018681

- Term: Anesthetics, General

- ID: D000000777

- Term: Anesthetics

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: AntiConv

- Name: Anticonvulsants

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M1666

- Name: Rocuronium

- Relevance: LOW

- As Found: Unknown

- ID: M18307

- Name: Propofol

- Relevance: HIGH

- As Found: Symptoms

- ID: M5241

- Name: Bromides

- Relevance: LOW

- As Found: Unknown

- ID: M1696

- Name: Remifentanil

- Relevance: LOW

- As Found: Unknown

- ID: M10043

- Name: Hypnotics and Sedatives

- Relevance: LOW

- As Found: Unknown

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M20766

- Name: Anesthetics, Intravenous

- Relevance: LOW

- As Found: Unknown

- ID: M20761

- Name: Anesthetics, General

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000015742

- Term: Propofol

### Misc Info Module

- Version Holder: 2024-05-31
