Evaluation of the Eleveld Pharmacokinetic Model for Propofol and Remifentanil in Cardiac Anesthesia with Cardiopulmonary Bypass

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

16 Feb 2025 → ongoing

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

The primary objective is to evaluate if there is a clinically significant difference between the measured and predicted concentrations during TCI of propofol and remifentanil using the Eleveld PK model. The median prediction error (MDPE) will be calculated to assess the performance of the Eleveld PK model during cardiac anesthesia. An MDPE between -20% and +20% is considered acceptable.

Secondary objectives 8

1. To evaluate the level of agreement between measured and predicted plasma concentrations of propofol and remifentanil during TCI using the Eleveld PK model.
2. To determine the median absolute prediction error (MDAPE) for the Eleveld PK model.
3. To compare MDPE, MDAPE and levels of agreement between the sevoflurane-remifentanil and propofol-remifentanil group.
4. To determine the adequacy of depth of anesthesia at different effect-site concentrations (CE ) of propofol and end-tidal concentrations and minimal alveolar concentration values for sevoflurane using the processed frontal EEG and the density spectral array provided by the Bispectral Index TM (BISTM ) monitoring system (Medtronic).
5. Evaluate the adequacy of analgesia at different C Eof remifentanil using the Nociception Level (NOL®) Index (Medtronic) at predetermined intraoperative time points.
6. Evaluate the adequacy of analgesia at different C Eof remifentanil using the Pupillary Pain Index (PPI, IDMED Algiscan®, Marseilles, France) at predetermined intraoperative time points.
7. Evaluate the agreement between the level of analgesia provided by NOL® and PPI.
8. Evaluate gender differences in performance of the Eleveld PK model during cardiac anesthesia

Conditions and MedDRA coding

Valvular heart disease; coronary heart disease; aortic disorders;

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. elective cardiac surgery with cardiopulmonary bypass
2. age ≥18 and ≤90 years
3. informed consent

Exclusion criteria 14

1. preoperative use of benzodiazepines (premedication or chronic use)
2. preoperative chronic use of opioids or chronic pain
3. emergency surgery
4. reoperations
5. preoperative hemodynamic instability requiring catecholamines
6. chronic severe renal insufficiency (≥G4 according to KDIGO 2012)
7. liver dysfunction with Child-Pugh Class B or C
8. planned hypothermic circulatory arrest
9. planned hypothermia on cardiopulmonary bypass <35°C
10. heart transplantation
11. left ventricular assist device implantation
12. cardioplegia with Custodiol® solution
13. contraindications to study drugs
14. pregnant women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the median prediction error (MDPE) for propofol and remifentanil concentrations.

Secondary endpoints 9

1. The agreement between measured and predicted propofol and remifentanil concentrations will be evaluated using Bland-Altman analysis.
2. The median absolute prediction error (MDAPE) will be calculated for propofol and remifentanil. An MDAPE <30% is considered clinically acceptable
3. The intraoperative area under the curve (AUC) for estimated and measured propofol and remifentanil concentrations will be compared. A difference of 20% will be considered clinically acceptable.
4. The BIS value at each sampling time point will be recorded. BIS values will be plotted against CE of propofol and SEVET to describe the distribution of BIS values at each CE and SEVET
5. BIS, SEF, SR and ST values will be recorded continuously. Descriptive statistics will be used to describe the percentage of time the BIS, SEF, SR and ST values were within the target range throughout anesthesia.
6. Descriptive statistics will be used to report the range of NOL values at each sampling time point. NOL values will be plotted against CE of remifentanil to describe the distribution of NOL values at each CE of remifentanil.
7. Descriptive statistics will be used to report the range of PPI values at each sampling time point. PPI values will be plotted against CE of remifentanil to describe the distribution of PPI values at each CE of remifentanil.
8. The agreement between analgesic depth provided by NOL® and PPI will be evaluated using Bland-Altman analysis.
9. After stratification for gender, MDPE and MDAPE will be compared between male and female patients (Mann-Whitney-U test).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University of Vienna

Sponsor organisation

Medical University of Vienna

Address

Waehringer Guertel 18-20, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University of Vienna

Contact name

Division of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine

Public contact point

Organisation

Medical University of Vienna

Contact name

Division of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications