Clinical trial NCT01096212: Efficacy and Safety of Sevofran in Patients Scheduled for Elective Surgery Under General Anesthesia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: General Anesthesia
Sevoflurane
Generic Drugs
Keywords: Efficacy
Minimum alveolar concentration
Safety
Sevoflurane
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: National Clinical Research Coordination Center, Seoul, Korea
First posted: 2010-03-31
Enrollment: 178
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Comparison of mean minimum alveolar concentration between original and generic sevoflurane
timeFrame: During mainenance of anesthesia under general anesthesia
Secondary outcomes:
measure: Comparison of secondary efficacy and safety endpoints between two inhalation agents
timeFrame: During maintenance of anesthesia under general anesthesia
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Sanggye-Paik Hospital
Study officials:
affiliation: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine
name: Gyu Jeong Noh, M.D. & Ph.D.
role: STUDY_CHAIR
affiliation: Department of Anesthesiology and Pain Medicine, Sanggye-Paik Hospital, College of Medicine, Inje University
name: Sang Seok Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.