Association Between Clinical Effect of Morphine With PCA After Surgery and Pharmacogenetics (PCA-Gene)

IRCCS Policlinico S. Matteo

Status: Completed

Conditions: Surgery; Anesthesia

Treatments: Drug: morphine chlorhydrate

Study type: Observational

Funder types: Other

Identifiers

NCT01233752

PT-SM-07-PCA-Gene

Details and patient eligibility

About

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.

Full 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.

Enrollment: 224 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females over 18 years, under 75 years, scheduled for postoperative pain control by PCA morphine administration
• HIV negative
• Classification American Society of Anesthesiologists (ASA) I: without systemic disease
• Classification ASA II or III (mild systemic disease or severe systemic disease that limits the activity without invalidity).
• Undergoing abdominal and urologic major surgery (neither urgent nor emergency surgery)
• Signed informed consent

Exclusion criteria

• Usual assumption of analgesic opioids
• Cognitive alterations nor mental retardation
• Severe hepatic/renal insufficiency (cholinesterase <3000 mU/ml, total bilirubinaemia <2 mg/dl and creatininaemia <1.2 mg/dl)
• Inpatients in intensive therapy, either with sedation and/or mechanic ventilation.
• Allergies to morphine and derivates

Trial design

224 participants in 2 patient groups

Group A

Description:

Homozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the more frequent allele of the polymorphism A118G of OPRM1 gene

Treatment:

Drug: morphine chlorhydrate

Group B

Description:

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

Treatment:

Drug: morphine chlorhydrate