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

March 30, 2010 updated by: Asan Medical Center

A Multi-center, Open-Label, Randomized, Active-controlled, Parallel, Phase 4 Clinical Trial to Assess the Efficacy and Safety of Sevofran in Patients Scheduled for Elective Surgery Under General Anesthesia

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center
      • Seoul, Korea, Republic of, 139-707
        • Sanggye-Paik Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Other Names:
  • Sevofran® (Hana Pharmacy, Co. Ltd, Seoul, Korea)
ACTIVE_COMPARATOR: origianl 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
Other Names:
  • Sevorane® (Abott Korea Ltd, Seoul, Korea)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of mean minimum alveolar concentration between original and generic sevoflurane
Time Frame: During mainenance of anesthesia under general anesthesia

Minimum alveolar concentration was determined by end-tidal sevoflurane concentrations. Mean MAC was calculated as following equation,

Mean MAC = (MAC * hour) / (maintenance time from administration of hypnotic agent (propofol) for acquring loss of consciousness to extubation)

During mainenance of anesthesia under general anesthesia

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of secondary efficacy and safety endpoints between two inhalation agents
Time Frame: During maintenance of anesthesia under general anesthesia

Secondary efficacy and safety characteristics include following items.

  1. Anesthesia exposure: MAC * hour [Time frame: maintenanane period of anesthesia]
  2. Bispectral index, BIS [Time frame: time to recovery of consciousnessn, time to recovery of orientation]
  3. Adverse event [Time frame: maintenanane period of anesthesia]
  4. Incidence and severity of postopertive nausea and vomiting [Time frame: 24 hours postoperatively]
  5. Concentrations of compound A, formaldehyde, methanol [Time frame: 30, 60, 90, 120, 150, 180 min after sevoflurane administration]
During maintenance of anesthesia under general anesthesia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Gyu Jeong Noh, M.D. & Ph.D., Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine
  • Principal Investigator: Sang Seok Lee, M.D., Department of Anesthesiology and Pain Medicine, Sanggye-Paik Hospital, College of Medicine, Inje University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

September 1, 2009

Study Completion (ACTUAL)

March 1, 2010

Study Registration Dates

First Submitted

March 29, 2010

First Submitted That Met QC Criteria

March 30, 2010

First Posted (ESTIMATE)

March 31, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

March 31, 2010

Last Update Submitted That Met QC Criteria

March 30, 2010

Last Verified

March 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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