Does Sevoflurane Cause Genomic Damage

NCT ID: NCT03109119

Last Updated: 2019-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-01

Study Completion Date

2019-12-31

Brief Summary

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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

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STUDY GOALS AND OBJECTIVES

1. To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair.
2. To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia.
3. 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

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Anesthesia; Adverse Effect

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Outcome Assessors
This is a double blinded study, where the participants are randomly selected using a computer - generated number and allocated to any one of the two groups. Both the patient and the outcome assessor will be blinded.

Study Groups

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Group S

These patients will be induced and maintained with sevoflurane during anaesthesia.

Group Type ACTIVE_COMPARATOR

Sevoflurane

Intervention Type DRUG

The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.

Group P

These patients will be induced and maintained with propofol during anaesthesia.

Group Type SHAM_COMPARATOR

Propofol

Intervention Type DRUG

These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.

Interventions

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Sevoflurane

The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.

Intervention Type DRUG

Propofol

These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.

Intervention Type DRUG

Other Intervention Names

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sevorane fresofol

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

12 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jubilee Mission Medical College and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vigil Peter, MD

Role: PRINCIPAL_INVESTIGATOR

Jubilee Mission Medical College and Research Institute, Thrissur, India

Locations

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Jubilee Mission Medical College and Research Institute

Thrissur, Kerala, India

Site Status RECRUITING

Countries

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India

Central Contacts

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Vigil Peter, MD

Role: CONTACT

918593821000

Alex George, PhD

Role: CONTACT

914872432200

Facility Contacts

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Vigil Peter, MD

Role: primary

918593821000

Alex George, PhD

Role: backup

914872432200

References

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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.

Reference Type RESULT
PMID: 15306730 (View on PubMed)

Musak 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.

Reference Type RESULT
PMID: 23525098 (View on PubMed)

Fenech 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.

Reference Type RESULT
PMID: 10517999 (View on PubMed)

Wiesner 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.

Reference Type RESULT
PMID: 18540930 (View on PubMed)

Tania 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

Reference Type RESULT

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.

Reference Type RESULT
PMID: 18023252 (View on PubMed)

Alcaraz 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.

Reference Type RESULT
PMID: 25386035 (View on PubMed)

Braz 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.

Reference Type RESULT
PMID: 21944903 (View on PubMed)

Other Identifiers

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08/16/IEC / JMMC&RI

Identifier Type: -

Identifier Source: org_study_id

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