Efficacy and Safety of Sevofran in Patients Scheduled for Elective Surgery Under General Anesthesia

NCT ID: NCT01096212

Last Updated: 2010-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-03-31

Brief Summary

Sevoflurane is currently being used in more than 100 countries worldwide with an estimated 100 million operations having been performed using sevoflurane as a general anesthetic. After the expiry of the patent on sevoflurane as a pharmaceutical drug, a generic product (Sevofran®; Hana pharmacy, Co. Ltd, Seoul, Korea) has been launched. The aims of this study were to investigate the efficacy (mean minimum alveolar concentration), recovery characteristics (time to recovery of consciousness (ROC) and recovery, and BIS values at ROC and orientation), and safety (incidence and severity of adverse events) of generic sevoflurane in patients undergoing elective surgery.

Detailed Description

Patients were randomly allocated to experimental group (generic sevoflurane) and active comparator group (original sevoflurane). Once in the operating room, patients were monitored with electrocardiography, non invasive blood pressure, pulse oximetry (Datex-Ohmeda S/5, Planar Systems, Inc., Beaverton, OR, USA) and BIS (Aspect 2000, Aspect Medical Systems, Inc., Newton, MA, USA).

Anesthesia was induced with fentanyl (2 μg/kg) and propofol (2mg/kg). When patients were unconscious, original or generic sevoflurane was administered. Tracheal intubation was facilitated by administering rocuronium 0.6 mg/kg. The lungs of the patients were then ventilated with oxygen in air (1:2), and the ventilation rate was adjusted to maintain the end-tidal carbon dioxide partial pressure between 35 and 45 mmHg. The concentrations of carbon dioxide, sevoflurane, and oxygen were measured continuously using an infrared anesthetic gas analyzer (Datex-Ohmeda S/5, Planar Systems, Inc., Beaverton, OR, USA), which was calibrated before anesthesia for each patient using a standard gas mixture.

The inspired concentration of sevoflurane was adjusted to maintain BIS values < 60 and stable haemodynamics (systolic arterial pressure (SAP) > 80 mmHg and heart rate (HR) > 45 beats/min). Also, it was titrated to prevent signs of inadequate anesthesia (sweating, facial flushing, movement and swallowing, HR > 90 beats/min without evidence of hypovolemia, and a 15 mmHg increase in SAP, compared with baseline SAP). Fentanyl 1 μg/kg was given if needed to resolve of signs of inadequate anesthesia.

Concentration of compound A, formaldehyde, and methadone were measured at preset interval: 30, 60, 90, 120, 150, 180 min after administration of sevoflurane. Blood and urine samples were taken at preset interval for analyzing concentration of inorganic fluoride: 1 hr after administration of sevoflurane and every 2 hr during maintenance of anesthesia.

Conditions

General Anesthesia; Sevoflurane; Generic Drugs

Keywords

Efficacy; Minimum alveolar concentration; Safety; Sevoflurane

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

generic sevoflurane

Group Type: EXPERIMENTAL

generic sevoflurane

Intervention Type: DRUG

Sevoflurane content: 99.99%, compound A: 3.8 ppm, water content (sample was opened, sealed and stored for 2 weeks) : 0.044% w/v

origianl sevoflurane

Group Type: ACTIVE_COMPARATOR

original sevoflurane

Intervention Type: DRUG

Sevoflurane content: 99.9985%, compound A: 4.6 ppm, water content (sample was opened, sealed and stored for 2 weeks): 0.072% w/v

Interventions

original sevoflurane

Sevoflurane content: 99.9985%, compound A: 4.6 ppm, water content (sample was opened, sealed and stored for 2 weeks): 0.072% w/v

Intervention Type: DRUG

generic sevoflurane

Sevoflurane content: 99.99%, compound A: 3.8 ppm, water content (sample was opened, sealed and stored for 2 weeks) : 0.044% w/v

Intervention Type: DRUG

Other Intervention Names

Sevorane® (Abott Korea Ltd, Seoul, Korea); Sevofran® (Hana Pharmacy, Co. Ltd, Seoul, Korea)

Eligibility Criteria

Inclusion Criteria

• Patients scheduled for elective surgery under general anesthesia
• American Society Anesthesiologists Physical Status (ASA PS) 1 or 2
• Aged 19 years or above

Exclusion Criteria

• ASA PS 3 or above
• aged under 19 years
• Contraindications against the use of sevoflurane
• Abnormal laboratory finding with clinical significance
• Evidence of pregnancy
• History of alcohol or drug abuse
• Hemoglobin < 11 mg/dl
• Neurological or psychiatric disease
• Unable or unwilling to give informed consent

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Clinical Research Coordination Center, Seoul, Korea

OTHER_GOV

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Asan Medical Center

Principal Investigators

Gyu Jeong Noh, M.D. & Ph.D.

Role: STUDY_CHAIR

Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine

Sang Seok Lee, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Anesthesiology and Pain Medicine, Sanggye-Paik Hospital, College of Medicine, Inje University

Locations

Asan Medical Center

Seoul, , South Korea

Sanggye-Paik Hospital

Seoul, , South Korea

Countries

South Korea

References

Byon HJ, Choi BM, Bang JY, Lee EK, Lee SS, Noh GJ. An Open-label Comparison of a New Generic Sevoflurane Formulation With Original Sevoflurane in Patients Scheduled for Elective Surgery Under General Anesthesia. Clin Ther. 2015 Apr 1;37(4):887-901. doi: 10.1016/j.clinthera.2015.01.012. Epub 2015 Feb 16.

Reference Type: DERIVED

PMID: 25697421 (View on PubMed)

Other Identifiers

Asan Medical Center_sevofran_1

Identifier Type: -

Identifier Source: org_study_id