Pharmacodynamic Differences Between Branded and Unbranded Remifentanil Molecules

Pharmacodynamic Differences Between Branded and Unbranded Remifentanil Molecules Available in Colombia for Tracheal Intubation of Adult Patients, 2012-2013

Unbranded drug molecules are produced after the patent of a given drug has expired. Unbranded molecules of Remifentanil have been marketed in Colombia, and several reports by anesthesiologist indicate that there are differences in the physiologic response of patients to these molecules. The investigators hypothesized that unbranded molecules of remifentanil require higher doses to obtain desired physiological responses as compared to the branded molecule.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Remifentanyl, Ultiva®; Drug: Fada Remifentanilo; Drug: Remifentanil Laboratorios Chalver de Colombia S.A.

Detailed Description

Introduction. Several remifentanil products are commercialized in Colombia while these have never been compared in a clinical setting.

Objective. The aim of this study was to investigate the pharmacodynamic profile of the innovative molecule of remifentanil (group O = Ultiva®) and two unbranded molecules (group A = Remifentanil Laboratorios Chalver de Colombia S.A. and group B = Fada Remifentanilo) registered in Colombia.

Methods. The investigators carried out a double-blind, randomized, controlled trial. The branded molecule of remifentanil (group O, n=29) was compared against the two unbranded molecules (group A, n=29; group B, n=32) during anesthetic induction and tracheal intubation in adult patients American Society of Anesthesiology Physical Status Classification = I without predictors for difficult airway. The target controlled infusion (TCI) doses evaluated were 6, 8 and 10 ng/ml with the Minto model. Induction was complemented with propofol 5 mg/ml (TCI) with the Schneider model and rocuronium 0.6 mg/kg. The primary outcome was defined as the difference in mean arterial pressure and heart rate pre-intubation (TCI equilibrium) and post-intubation (maximum measurement within 5 minutes).

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 11001000
      • Fundación Universitaria de Ciencias de la Salud, Hospital de San Jose

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients requiring orotracheal intubation
• 18-50 years old
• Body mass index <31 kg/m2
• Written informed consent

Exclusion Criteria:

• Pregnancy
• Risk of difficult airway
• History of opioid use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group O; Remifentanyl innovative molecule = Ultiva®	Drug: Remifentanyl, Ultiva®; Anesthetic induction for orotracheal intubation. Group O; Drug: Fada Remifentanilo; Anesthetic induction for orotracheal intubation. Group B
Active Comparator: Group A; Remifentanyl comparator A = Remifentanil Laboratorios Chalver de Colombia S.A.	Drug: Fada Remifentanilo; Anesthetic induction for orotracheal intubation. Group B; Drug: Remifentanil Laboratorios Chalver de Colombia S.A.; Anesthetic induction for orotracheal intubation. Group A
Active Comparator: Group B; Remifentanyl comparator B = Fada Remifentanilo	Drug: Remifentanyl, Ultiva®; Anesthetic induction for orotracheal intubation. Group O; Drug: Remifentanil Laboratorios Chalver de Colombia S.A.; Anesthetic induction for orotracheal intubation. Group A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome of heart rate or mean arterial pressure difference before and after tracheal intubation	Heart rate measured with EKG. Mean arterial pressure measured with automatic blood pressure cuff.	Average of 5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cooper intubation condition score	Jaw relaxation: 0 poor, 1 minimum, 2 moderate, 3 good. Vocal cords: 0 closed, 1 closing, 2 moving, 3 open. Intubation response: 0 severe cough, 1 mild cough, 2 mild diaphragmatic movement, 3 no response. Cooper score: Jaw relaxation + Vocal cords + Intubation response	Measured during tracheal intubation, average of 30 seconds

Collaborators and Investigators

• Sponsor: Fundación Universitaria de Ciencias de la Salud
• Collaborators: Hospital de San Jose
• Investigators: Principal Investigator: luis e reyes, professor, Fundación Universitaria de Ciencias de la Salud

Publications and helpful links

General Publications

• Kwak HJ, Min SK, Kim DH, Kang M, Kim JY. Effect-site concentration of remifentanil for nasotracheal versus orotracheal intubation during target-controlled infusion of propofol. J Int Med Res. 2011;39(5):1816-23. doi: 10.1177/147323001103900524.
• Lysakowski C, Dumont L, Pellegrini M, Clergue F, Tassonyi E. Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia. Br J Anaesth. 2001 Apr;86(4):523-7. doi: 10.1093/bja/86.4.523.
• Coskun D, Celebi H, Karaca G, Karabiyik L. Remifentanil versus fentanyl compared in a target-controlled infusion of propofol anesthesia: quality of anesthesia and recovery profile. J Anesth. 2010 Jun;24(3):373-9. doi: 10.1007/s00540-010-0898-1. Epub 2010 Mar 13.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 28, 2014
• First Posted (Estimate): January 29, 2014

Study Record Updates

• Last Update Posted (Estimate): January 29, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: propofol; remifentanil; pharmacodynamic; heart rate; orotracheal intubation; total intravenous anesthesia; mean arterial pressure; Cooper intubation condition score
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: 326-3847-22