Clinical trial NCT01233752: Association Between Clinical Effect of Morphine With PCA After Surgery and Pharmacogenetics
Official title: Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anesthesia
Surgery
Keywords: systemic morphine analgesia
pharmacogenetics
pharmacokinetics
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2010-11-03
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pazients scheduled for major abdominal or urological surgery with postoperative pain control by PCA morphine administration

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: first 24 h after surgery
Secondary outcomes:
measure: Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure
timeFrame: during 24 h postsurgery
measure: Detection of the medium morphine dose
timeFrame: First 24 h after surgery
measure: Pharmacokinetics of morphine with PCA after surgery
timeFrame: 48 h after surgery
measure: Variants frequency at loci OPRM1, COMT, UGTs, ESR1
timeFrame: Within 48h after surgery
measure: Detection of the possible side effects.
timeFrame: 72 h postopratively
measure: Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects).
timeFrame: within 72 h postoperatively
Other outcomes:
Locations:
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
Study officials:
affiliation: IRCCS Policlinico San Matteo
name: Massimo Allegri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cattaneo S, Ingelmo P, Scudeller L, Gregori M, Bugada D, Baciarello M, Marchesini M, Alberio G, Normanno M, Jotti GS, Meschi T, Fanelli G, Massimo A. Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery. J Opioid Manag. 2017 Mar/Apr;13(2):85-94. doi: 10.5055/jom.2017.0372.
citation: De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, Molinaro V, Garbin G, Ranzani GN, Alberio G, Normanno M, Lovisari F, Somaini M, Govoni S, Mura E, Bugada D, Niebel T, Zorzetto M, De Gregori S, Molinaro M, Fanelli G, Allegri M. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628-36. doi: 10.1016/j.jpain.2016.02.003. Epub 2016 Feb 21.