General AnesthesiaPhase 4NCT01096212
Efficacy and Safety of Sevofran in Patients Scheduled for Elective Surgery Under General Anesthesia
A Phase 4 study testing original sevoflurane and generic sevoflurane in people with General Anesthesia and Sevoflurane, run by Asan Medical Center at 2 sites in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- General Anesthesia, Sevoflurane, Generic Drugs
- What is being tested?
- original sevoflurane and generic sevoflurane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 2 sitesSouth Korea
- Study dates
- Sep 2008to Mar 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients scheduled for elective surgery under general anesthesia
- American Society Anesthesiologists Physical Status (ASA PS) 1 or 2
- Aged 19 years or above
Who cannot join
- 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
Show all 9Show fewer
- Hemoglobin < 11 mg/dl
- Neurological or psychiatric disease
- Unable or unwilling to give informed consent
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites
Asan Medical Center
Seoul, 138-736
Sanggye-Paik Hospital
Seoul, 139-707
About this study
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
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.
Read the 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
- Being tested
- original sevoflurane, generic sevoflurane
- Keywords
- Efficacy, Minimum alveolar concentration, Safety, Sevoflurane
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
original sevofluraneDrug
Also called Sevorane® (Abott Korea Ltd, Seoul, Korea)
Sevoflurane content: 99.9985%, compound A: 4.6 ppm, water content (sample was opened, sealed and stored for 2 weeks): 0.072% w/v
generic sevofluraneDrug
Also called Sevofran® (Hana Pharmacy, Co. Ltd, Seoul, Korea)
Sevoflurane content: 99.99%, compound A: 3.8 ppm, water content (sample was opened, sealed and stored for 2 weeks) : 0.044% w/v
| Study group | Role | What they receive |
|---|---|---|
| generic sevoflurane | Experimental | Not described Receives: Drug: generic sevoflurane |
| origianl sevoflurane | Active comparator | Not described Receives: Drug: original sevoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of mean minimum alveolar concentration between original and generic sevoflurane
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)
Measured: During mainenance of anesthesia under general anesthesia
Secondary outcomes (1)
Comparison of secondary efficacy and safety endpoints between two inhalation agents
Secondary efficacy and safety characteristics include following items.
- Anesthesia exposure: MAC * hour [Time frame: maintenanane period of anesthesia]
- Bispectral index, BIS [Time frame: time to recovery of consciousnessn, time to recovery of orientation]
- Adverse event [Time frame: maintenanane period of anesthesia]
- Incidence and severity of postopertive nausea and vomiting [Time frame: 24 hours postoperatively]
- Concentrations of compound A, formaldehyde, methanol [Time frame: 30, 60, 90, 120, 150, 180 min after sevoflurane administration]
Measured: During maintenance of anesthesia under general anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2010 (estimated)
- Study startSep 2008
- Primary completionSep 2009
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for General AnesthesiaStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Clinical Research Coordination Center, Seoul, Korea
- Investigators
- Gyu Jeong Noh, M.D. & Ph.D., Study chair, Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of MedicineSang Seok Lee, M.D., Principal investigator, Department of Anesthesiology and Pain Medicine, Sanggye-Paik Hospital, College of Medicine, Inje University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01096212
- Sponsor's protocol ID
- Asan Medical Center_sevofran_1
- Status last verified
- Mar 2010
- First submitted
- 29 Mar 2010
- Last updated
- 31 Mar 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25697421
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01096212
- Acronym / sponsor ID
- Asan Medical Center_sevofran_1
- Conditions
- General Anesthesia, Sevoflurane, Generic Drugs
- Keywords
- Efficacy, Minimum alveolar concentration, Safety, Sevoflurane
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Collaborators
- National Clinical Research Coordination Center, Seoul, Korea
- Study start
- Sep 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 31 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| generic sevoflurane | Experimental | Drug: generic sevoflurane |
| origianl sevoflurane | Active comparator | Drug: original sevoflurane |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients scheduled for elective surgery under general anesthesia
- American Society Anesthesiologists Physical Status (ASA PS) 1 or 2
- Aged 19 years or above
Key exclusion criteria (9 listed)
- ASA PS 3 or above
- aged under 19 years
- Contraindications against the use of sevoflurane
- Abnormal laboratory finding with clinical significance
- Evidence of pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| original sevofluraneAlso: Sevorane® (Abott Korea Ltd, Seoul, Korea)Sevoflurane content: 99.9985%, compound A: 4.6 ppm, water content (sample was opened, sealed and stored for 2 weeks): 0.072% w/v | Drug | origianl sevoflurane |
| generic sevofluraneAlso: Sevofran® (Hana Pharmacy, Co. Ltd, Seoul, Korea)Sevoflurane content: 99.99%, compound A: 3.8 ppm, water content (sample was opened, sealed and stored for 2 weeks) : 0.044% w/v | Drug | generic sevoflurane |
Primary outcome
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)
1 secondary outcome
Comparison of secondary efficacy and safety endpoints between two inhalation agents
Time frame: During maintenance of anesthesia under general anesthesia
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2010.
- Derived from this study: PubMed 25697421Byon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gyu Jeong Noh, M.D. & Ph.D. study chair
Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine
Sang Seok Lee, M.D. principal investigator
Department of Anesthesiology and Pain Medicine, Sanggye-Paik Hospital, College of Medicine, Inje University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing original sevoflurane and generic sevoflurane in people with General Anesthesia and Sevoflurane, run by Asan Medical Center at 2 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of mean minimum alveolar concentration between original and generic sevoflurane (time frame: During mainenance of anesthesia under general anesthesia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01096212, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2010.