Anesthesia; Adverse EffectPhase 4NCT03109119
Does Sevoflurane Cause Genomic Damage
A Phase 4 study testing Sevoflurane and Propofol in people with Anesthesia; Adverse Effect, run by Jubilee Mission Medical College and Research Institute at 1 site in India.
Trial summary
This study aims to find out if sevoflurane causes any cell damage to patients undergoing general anaesthesia. In case of any damage, the reversibility of the damage is also assessed. Read more about this study
- Who is it for?
- Ages 6 to 12 months
- Conditions the study is for
- Anesthesia; Adverse Effect
- What is being tested?
- Sevoflurane and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteIndia
- Study dates
- 1 Sep 2018to Dec 2019
- 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 6 to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children must have isolated cleft lip or palate.
- The surgery must be a primary repair of cleft lip or palate.
- The minimum duration of the surgery must be 90 minutes.
Who cannot join
- Children who have undergone previous surgery.
- Children who have syndromic cleft lip or palate.
- Children with bleeding disorders.
- Children with known allergy to any of the concerned drugs.
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Jubilee Mission Medical College and Research Institute
Thrissur, Kerala, 680005
Vigil Peter, MD, 918593821000, drpeteralapatt@gmail.com
Alex George, PhD, 914872432200, alexgeorge@jmmc.ac.in
About this study
Official title: Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?
This study aims to find out if sevoflurane causes any cell damage to patients undergoing general anaesthesia. In case of any damage, the reversibility of the damage is also assessed. This is a prospective, comparative study carried out in all children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery under Smile Train organisation ìn our hospital,who satisfy the inclusion and exclusion criteria.
Read the detailed description
STUDY GOALS AND OBJECTIVES
- To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair.
- To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia.
- To evaluate the reversibility of the induced genomic instability when exposure is discontinued.
STUDY DESIGN Type of study : Prospective Comparative Study Research population : All children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery of our hospital, who satisfy the inclusion and exclusion criteria.
Sample Size : A total of 30 children will be enrolled for the study. METHODOLOGY Children scheduled to undergo surgical repair of cleft lip or palate were enrolled for the study, after addressing the inclusion and exclusion criteria.
A peripheral blood sample of 1.5 ml (S-1) will be taken before the induction of anaesthesia .All children will be randomly allocated into two groups - group S and P.All children will be premedicated with Inj.Glycopyrolate 0.01 mg/kg . Children in group S will be induced with sevoflurane, whereas children in group P will be induced with propofol.All children will be intubated using I / V Vecuronium 0.1 mg / kg .Analgesia will be provided using I / V Fentanyl 1.5 mcg / kg. Depth of anaesthesia will be maintained with sevoflurane in group S and with propofol infusion in group P. The vitals will be monitored as usual intraop and the children will be extubated at the end of the surgery.
Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day All the blood samples will be evaluated for genomic instability using Alkaline Comet Assay by the Genetics Lab of our hospital.
STATISTICAL ANALYSIS
The findings of this study will be analysed using Chi-square test, Student's t-test, Mann-Whitney U test, mean and standard deviation to yield the final results. The study will be considered statistically significant with a p value of less than 0.05
- Conditions
- Anesthesia; Adverse Effect
- Being tested
- Sevoflurane, Propofol
- Keywords
- genomic instability, Sevoflurane, General anaesthesia
- Medical subject headings
- Genomic Instability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevofluraneDrug
Also called sevorane
The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.
PropofolDrug
Also called fresofol
These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.
| Study group | Role | What they receive |
|---|---|---|
| Group S | Active comparator | These patients will be induced and maintained with sevoflurane during anaesthesia. Receives: Drug: Sevoflurane |
| Group P | Sham comparator | These patients will be induced and maintained with propofol during anaesthesia. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genomic instability
Genomic instability will be assessed using comet assay
Measured: It will be assessed at 2 hours after anaesthesia.
Genomic instability
Genomic instability will be assessed using comet assay.
Measured: It will be assessed 48 hours after anaesthesia.
Secondary outcomes (2)
Reversibility of the genomic instability
Assessed using comet assay
Measured: It will be assessed on fifth day after anaesthesia.
Reversibility of genomic instability
It will be assessed using comet assay.
Measured: It will be assessed on the 14th day after anaesthesia.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2017
- Study start1 Sep 2018
- Primary completionSep 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Anesthesia; Adverse EffectStudies of the same condition, open and under way.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All children will be randomly allocated into two groups - group S and P. Children in group S will be anaesthetised with sevoflurane, whereas children in group P will be anaesthetised with propofol. Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day. These blood samples will be evaluated for genomic instability using Alkaline Comet Assay and micronucleus test by the Genetics Lab of our hospital.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jubilee Mission Medical College and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vigil Peter, MD, Principal investigator, Jubilee Mission Medical College and Research Institute, Thrissur, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03109119
- Sponsor's protocol ID
- 08/16/IEC / JMMC&RI
- Status last verified
- Jan 2019
- First submitted
- 20 Mar 2017
- Last updated
- 14 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jaloszynski P. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet. 2004;45(3):369-74.
PubMed 15306730Musak L, Smerhovsky Z, Halasova E, Osina O, Letkova L, Vodickova L, Polakova V, Buchancova J, Hemminki K, Vodicka P. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Work Environ Health. 2013 Nov;39(6):618-30. doi: 10.5271/sjweh.3358. Epub 2013 Mar 22.
PubMed 23525098Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 1999 Jul 16;428(1-2):271-83. doi: 10.1016/s1383-5742(99)00053-8.
PubMed 10517999Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008 Aug;63(8):861-4. doi: 10.1111/j.1365-2044.2008.05498.x. Epub 2008 Jun 6.
PubMed 18540930Tania K.de Araujo, Roseane L, Flora M.B.B, Nilson C.R, Cristina W.P, Ricardo Manoel da Cruz et al-Genotoxic effects of anaesthetics in OT personnel evaluated by micronuclei tests Journal of Anaesthesia and Clinical Science ISSN 2049-9752,10.7243/2049-9752-2-26,2013
Rozgaj R, Kasuba V, Brozovic G, Jazbec A. Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health. 2009 Jan;212(1):11-7. doi: 10.1016/j.ijheh.2007.09.001. Epub 2007 Nov 26.
PubMed 18023252Alcaraz M, Quesada S, Armero D, Martin-Gil R, Olivares A, Achel GD. Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation. Colomb Med (Cali). 2014 Sep 30;45(3):104-9. eCollection 2014 Jul-Sep.
PubMed 25386035Braz MG, Braz LG, Barbosa BS, Giacobino J, Orosz JE, Salvadori DM, Braz JR. DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia. Mutat Res. 2011 Dec 24;726(2):251-4. doi: 10.1016/j.mrgentox.2011.09.007. Epub 2011 Sep 16.
PubMed 21944903
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?
- ClinicalTrials.gov ID
- NCT03109119
- Acronym / sponsor ID
- 08/16/IEC / JMMC&RI
- Conditions
- Anesthesia; Adverse Effect
- Keywords
- genomic instability, Sevoflurane, General anaesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Jubilee Mission Medical College and Research InstituteUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- Sep 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 12 Apr 2017 (actual)
- 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.
This study aims to find out if sevoflurane causes any cell damage to patients undergoing general anaesthesia. In case of any damage, the reversibility of the damage is also assessed. This is a prospective, comparative study carried out in all children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery under Smile Train organisation ìn our hospital,who satisfy the inclusion and exclusion criteria.
Detailed description
STUDY GOALS AND OBJECTIVES
- To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair.
- To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia.
- To evaluate the reversibility of the induced genomic instability when exposure is discontinued.
STUDY DESIGN Type of study : Prospective Comparative Study Research population : All children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery of our hospital, who satisfy the inclusion and exclusion criteria.
Sample Size : A total of 30 children will be enrolled for the study. METHODOLOGY Children scheduled to undergo surgical repair of cleft lip or palate were enrolled for the study, after addressing the inclusion and exclusion criteria.
A peripheral blood sample of 1.5 ml (S-1) will be taken before the induction of anaesthesia .All children will be randomly allocated into two groups - group S and P.All children will be premedicated with Inj.Glycopyrolate 0.01 mg/kg . Children in group S will be induced with sevoflurane, whereas children in group P will be induced with propofol.All children will be intubated using I / V Vecuronium 0.1 mg / kg .Analgesia will be provided using I / V Fentanyl 1.5 mcg / kg. Depth of anaesthesia will be maintained with sevoflurane in group S and with propofol infusion in group P. The vitals will be monitored as usual intraop and the children will be extubated at the end of the surgery.
Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day All the blood samples will be evaluated for genomic instability using Alkaline Comet Assay by the Genetics Lab of our hospital.
STATISTICAL ANALYSIS
The findings of this study will be analysed using Chi-square test, Student's t-test, Mann-Whitney U test, mean and standard deviation to yield the final results. The study will be considered statistically significant with a p value of less than 0.05
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- All children will be randomly allocated into two groups - group S and P. Children in group S will be anaesthetised with sevoflurane, whereas children in group P will be anaesthetised with propofol. Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day. These blood samples will be evaluated for genomic instability using Alkaline Comet Assay and micronucleus test by the Genetics Lab of our hospital.
| Arm | Type | Receives |
|---|---|---|
| Group S | Active comparator | Drug: SevofluraneThese patients will be induced and maintained with sevoflurane during anaesthesia. |
| Group P | Sham comparator | Drug: PropofolThese patients will be induced and maintained with propofol during anaesthesia. |
Who may qualify
- Ages
- 6 to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children must have isolated cleft lip or palate.
- The surgery must be a primary repair of cleft lip or palate.
- The minimum duration of the surgery must be 90 minutes.
Key exclusion criteria (4 listed)
- Children who have undergone previous surgery.
- Children who have syndromic cleft lip or palate.
- Children with bleeding disorders.
- Children with known allergy to any of the concerned drugs.
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 |
|---|---|---|
| SevofluraneAlso: sevoraneThe patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia. | Drug | Group S |
| PropofolAlso: fresofolThese patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion. | Drug | Group P |
Primary outcome
Genomic instability
Time frame: It will be assessed at 2 hours after anaesthesia.
Genomic instability will be assessed using comet assay
Genomic instability
Time frame: It will be assessed 48 hours after anaesthesia.
Genomic instability will be assessed using comet assay.
2 secondary outcomes
Reversibility of the genomic instability
Time frame: It will be assessed on fifth day after anaesthesia.
Reversibility of genomic instability
Time frame: It will be assessed on the 14th day after anaesthesia.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2019.
- Results publication: PubMed 15306730Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jaloszynski P. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet. 2004;45(3):369-74.
- Results publication: PubMed 23525098Musak L, Smerhovsky Z, Halasova E, Osina O, Letkova L, Vodickova L, Polakova V, Buchancova J, Hemminki K, Vodicka P. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Work Environ Health. 2013 Nov;39(6):618-30. doi: 10.5271/sjweh.3358. Epub 2013 Mar 22.
- Results publication: PubMed 10517999Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 1999 Jul 16;428(1-2):271-83. doi: 10.1016/s1383-5742(99)00053-8.
- Results publication: PubMed 18540930Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008 Aug;63(8):861-4. doi: 10.1111/j.1365-2044.2008.05498.x. Epub 2008 Jun 6.
- Results publicationTania K.de Araujo, Roseane L, Flora M.B.B, Nilson C.R, Cristina W.P, Ricardo Manoel da Cruz et al-Genotoxic effects of anaesthetics in OT personnel evaluated by micronuclei tests Journal of Anaesthesia and Clinical Science ISSN 2049-9752,10.7243/2049-9752-2-26,2013
- Results publication: PubMed 18023252Rozgaj R, Kasuba V, Brozovic G, Jazbec A. Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health. 2009 Jan;212(1):11-7. doi: 10.1016/j.ijheh.2007.09.001. Epub 2007 Nov 26.
- Results publication: PubMed 25386035Alcaraz M, Quesada S, Armero D, Martin-Gil R, Olivares A, Achel GD. Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation. Colomb Med (Cali). 2014 Sep 30;45(3):104-9. eCollection 2014 Jul-Sep.
- Results publication: PubMed 21944903Braz MG, Braz LG, Barbosa BS, Giacobino J, Orosz JE, Salvadori DM, Braz JR. DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia. Mutat Res. 2011 Dec 24;726(2):251-4. doi: 10.1016/j.mrgentox.2011.09.007. Epub 2011 Sep 16.
- Individual participant dataSharing planned: No
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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.
Vigil Peter, MD principal investigator
Jubilee Mission Medical College and Research Institute, Thrissur, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sevoflurane and Propofol in people with Anesthesia; Adverse Effect, run by Jubilee Mission Medical College and Research Institute at 1 site in India.
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 4 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: status not confirmed, as of the sponsor's last update on 14 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vigil Peter, MD (918593821000, drpeteralapatt@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genomic instability (time frame: It will be assessed at 2 hours after anaesthesia.). The study lists 2 primary outcomes in all. 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 NCT03109119, which also lists 8 linked publications.
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 14 Jan 2019.