Therapeutic Equivalence (TE) Study of Propofol 2% MCT Fresenius (MCT=Medium-Chain Triglycerides) Compared With Diprivan® in Patients Undergoing Elective Surgery (PropofolTE)

Therapeutic Equivalence Study of Propofol Using Target-Controlled Infusion of Propofol 2% (20 mg/mL) MCT Fresenius Compared With Diprivan® 20 mg/mL (AstraZeneca) in Patients Undergoing Elective Surgery

The purpose of this study is to evaluate the therapeutic equivalence, based on pharmacodynamic parameters of Propofol 2% (20 mg/mL) MCT Fresenius and Diprivan® 20 mg/mL (AstraZeneca), administered by target controlled infusion (TCI).

Study Overview

• Status: Completed
• Conditions: General Anesthesia; Elective Surgery
• Intervention / Treatment: Drug: Propofol; Drug: Diprivan

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • CHU de Bordeaux, Groupe hospitalier Pellegrin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects ≥18 years and <65 years old
2. Able to understand and give signed and dated written informed consent
3. Body mass index (BMI) ≥20 and ≤30 kg/m² at screening
4. ASA (American Society of Anesthesiologists) physical status 1 or 2
5. Undergoing elective, minor orthopedic, vascular, urological, or gynecological surgery
6. Patients should be affiliated to a social security scheme and benefit from the corresponding rights and cover

Exclusion Criteria:

1. The following planned procedures are to be excluded:

   • Day surgery
   • Emergency surgery
   • Total hip or total knee replacement
   • Requiring opening of the great cavities of the body (cranium, thorax, peritoneum, or pelvis)
   • With routine risk, even if low, of hemorrhage severe enough to require administration of colloid or blood products
   • With routine risk, even if low, of death during or soon after the procedure
   • Vascular surgery involving the aorta, venae cavae, iliac arteries, or femoral arteries
2. Intended administration of IV medications through a central venous catheter (Note: a central venous catheter may be used to obtain Pharmacokinetic (PK) samples, though only if no port of the catheter is being used for administration of any other product, including crystalloid infusion at more than a "keep line open" rate)
3. Administration of general anesthesia or propofol within the 7 days prior to randomization
4. History of hypersensitivity to propofol, eggs, soya, peanuts, or any other constituent of the study drugs
5. ASA physical status ≥3

6. History of major anesthesia complications including, but not limited to:

   • Clinically significant hypoxia
   • Profound hypotension
   • Anaphylaxis or anaphylactic reactions
   • Unpredictable anesthesia agent requirements

7. History of difficult airway management including, but not limited to:

   • Problematic artificial ventilation with face mask
   • Repeated difficulty of placement of laryngeal mask airway (LMA)
   • Difficult laryngeal intubation (Cormack-Lehane grade 3 to 4) and requiring alternative technique e.g. fibre-optic or awake laryngeal intubation
8. History of difficult venous access
9. Myocardial infarction within 6 months of randomization or a cardiac reperfusion procedure within 6 weeks of randomization
10. Significant respiratory, cardiovascular, liver or renal disease as assessed by investigator
11. Active systemic infection (localized infection related to surgical procedure is allowable as long as there is no indication of systemic involvement)
12. History of psychiatric disorder, including use of sedatives or antidepressants for any reason, within 6 months prior to randomization
13. Alcohol or other substance abuse within 2 years prior to randomization, as well as for the duration of the study
14. Use of medication that could reduce the subject's respiratory and/or cardiac output
15. Female subjects who are pregnant, breastfeeding, or lactating
16. Hemoglobin <7.5 g/dL at screening or randomization
17. Platelets <50,000 x 10³/μL at screening or randomization
18. ECG findings detected at screening not consistent with the subject's medical history or warranting cardiology review
19. Participation in an interventional clinical study within 6 months of screening
20. History of Propofol infusion syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Diprivan® 20 mg/mL (AstraZeneca); Dosage form: lipid emulsion Dosage: Initial effect-site target concentration: 5 μg/mL, if necessary increased by 1 μg/mL every 60 seconds until LOER Frequency: continuously (will be adjusted to keep Bispectral Index (BIS) between 40 and 60, however maintenance target concentration can be increased if a patient needs a BIS <40 with regard to individual condition and the respective surgery) Duration: Until end of surgery	Drug: Diprivan
EXPERIMENTAL: Propofol 2% (20 mg/mL) MCT Fresenius; Dosage form: lipid emulsion Dosage: Initial effect-site target concentration: 5 μg/mL, if necessary increased by 1 μg/mL every 60 seconds until LOER Frequency: continuously (will be adjusted to keep Bispectral Index (BIS) between 40 and 60, however maintenance target concentration can be increased if a patient needs a BIS <40 with regard to individual condition and the respective surgery) Duration: Until end of surgery	Drug: Propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Loss of Eyelash Reflex (LOER)	The overall timeframe until LOER is observed depends on the patient and varies from only a few seconds up to 240 seconds in total.	Every ten seconds from the initiation of TCI anesthesia device until LOER occurs up to 150 seconds. If LOER has not occurred within this timeframe, target propofol concentration to be increased by 1 μg/mL every 60 seconds until LOER is observed.

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Collaborators: Quintiles, Inc.
• Investigators: Principal Investigator: Francois Sztark, Professor, CHU de Bordeaux, Groupe hospitalier Pellegrin

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: May 8, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (ESTIMATE): May 20, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 21, 2014
• Last Update Submitted That Met QC Criteria: February 20, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Propofol; Therapeutic Equivalence
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: PROP-001-CP3; 2012-005701-43 (EUDRACT_NUMBER)