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

Fresenius Kabi

Status and phase: Completed; Phase 3

Conditions: Elective Surgery; General Anesthesia

Treatments: Drug: Propofol; Drug: Diprivan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01856998

PROP-001-CP3

2012-005701-43 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 71 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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71 participants in 2 patient groups

Diprivan® 20 mg/mL (AstraZeneca)

Active Comparator group

Description:

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

Treatment:

Drug: Diprivan

Propofol 2% (20 mg/mL) MCT Fresenius

Experimental group

Description:

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

Treatment:

Drug: Propofol