Clinical trial NCT03109119: Does Sevoflurane Cause Genomic Damage
Official title: Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anesthesia; Adverse Effect
Keywords: genomic instability
Sevoflurane
General anaesthesia
Lead sponsor: Jubilee Mission Medical College and Research Institute
Sponsor class: OTHER
First posted: 2017-04-12
Enrollment: 30
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

Brief 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. 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Genomic instability
timeFrame: It will be assessed at 2 hours after anaesthesia.
measure: Genomic instability
timeFrame: It will be assessed 48 hours after anaesthesia.
Secondary outcomes:
measure: Reversibility of the genomic instability
timeFrame: It will be assessed on fifth day after anaesthesia.
measure: Reversibility of genomic instability
timeFrame: It will be assessed on the 14th day after anaesthesia.
Other outcomes:
Locations:
city: Thrissur
country: India
facility: Jubilee Mission Medical College and Research Institute
state: Kerala
Study officials:
affiliation: Jubilee Mission Medical College and Research Institute, Thrissur, India
name: Vigil Peter, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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