Association Between Clinical Effect of Morphine With PCA After Surgery and Pharmacogenetics

Completed

• Conditions: Anesthesia; Surgery
• Interventions: Drug: morphine chlorhydrate

• Registration Number: NCT01233752
• Lead Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Brief Summary

Identification of the genetic polymorphisms that could be correlated either with a better clinical response or with a major predisposition of patients to develop tolerance and/or side effects to the treatment with morphine.

Detailed Description

Valuation of the medium morphine dose (mg/kg/die) necessary to maintain NRS\<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).

In order to avoid the bias related to alterations in metabolism, patients with Cmax and AUC of morphine (and metabolites M6G and M3G) \>2 standard deviation higher than expected population curve ("outliers") will be excluded for the primary purpose.

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-11-02
• Study First Submitted QC: 2010-11-02
• Study First Posted: 2010-11-03
• Status Verified: 2013-07
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Last Update Submitted: 2013-07-18
• Last Update Posted: 2013-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 224

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group B	morphine chlorhydrate	Both homozygous and heterozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the less frequent allele of the polymorphism A118G of OPRM1 gene
Group A	morphine chlorhydrate	Homozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the more frequent allele of the polymorphism A118G of OPRM1 gene

Primary Outcome Measures

Name	Time	Method
Assessment of the medium morphine dose (mg/kg/die)in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele	first 24 h after surgery	Valutation of the medium morphine dose (mg/kg/die) necessary to maintain NRS\<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of morphine with PCA after surgery	48 h after surgery	Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).
Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure	during 24 h postsurgery	Frequency of the variants at the loci OPRM1, COMT, UGTs, ESR1, both in patients with NRS ≤4 and in those having NRS \>4 at least once during 24 hours.
Variants frequency at loci OPRM1, COMT, UGTs, ESR1	Within 48h after surgery	Variants frequency at loci OPRM1, COMT, UGTs, ESR1 in the patients with Cmax and AUC of both morphine and M3G-M6G metabolites \>2 standard deviations higher than expected population curve ("outliers").
Detection of the medium morphine dose	First 24 h after surgery	Detection of the medium morphine dose (mg/kg/die) necessary to maintain NRS\<4 though the first 48 hours after surgery.
Detection of the possible side effects.	72 h postopratively
Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects).	within 72 h postoperatively

Trial Locations

Locations (2)

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliera San Gerardo; 🇮🇹 Monza, Italy