Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.
Overview
- Phase
- Not Applicable
- Intervention
- morphine chlorhydrate
- Conditions
- Anesthesia
- Sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Enrollment
- 224
- Locations
- 2
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Massimo Allegri
MD
Fondazione IRCCS Policlinico San Matteo di Pavia
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group A
Homozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the more frequent allele of the polymorphism A118G of OPRM1 gene
Intervention: morphine chlorhydrate
Group B
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
Intervention: morphine chlorhydrate
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- Pharmacokinetics of morphine with PCA after surgery(48 h after surgery)
- Variants frequency at loci OPRM1, COMT, UGTs, ESR1(Within 48h after surgery)
- Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure(during 24 h postsurgery)
- Detection of the medium morphine dose(First 24 h 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)