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

NCT ID: NCT01233752

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 224 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-07-31

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.

Conditions

Anesthesia; Surgery

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

morphine chlorhydrate

Intervention Type: DRUG

The drug will be administrated by a bolus 45 minutes before the end of the surgery, with the following modalities: bolus with morphine chlorhydrate 0.15 mg/kg ± 20%. Also acetaminophene 1g and ketoprofen 160 mg (ketorolac 30mg) will be administrated during the operation.

At the exit of the operative compartment patients will have an electronic pump (PCA) for 48h with morphine chlorhydrate to be used in boluses by 1 mg with a lock out of 5 mins, max dose 20 mg in 4 hours.

Moreover, ketoprofen will be prescribed 160 mg x 2 per day (ketorolac 30mg x 2) (in case of allergy acetaminophene 1g x 3 daily).

Postoperative analgesic treatment is lasting 48h for each patient (between starting of the PCA infusion (T0) and the following 48h).

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

morphine chlorhydrate

Intervention Type: DRUG

The drug will be administrated by a bolus 45 minutes before the end of the surgery, with the following modalities: bolus with morphine chlorhydrate 0.15 mg/kg ± 20%. Also acetaminophene 1g and ketoprofen 160 mg (ketorolac 30mg) will be administrated during the operation.

At the exit of the operative compartment patients will have an electronic pump (PCA) for 48h with morphine chlorhydrate to be used in boluses by 1 mg with a lock out of 5 mins, max dose 20 mg in 4 hours.

Moreover, ketoprofen will be prescribed 160 mg x 2 per day (ketorolac 30mg x 2) (in case of allergy acetaminophene 1g x 3 daily).

Postoperative analgesic treatment is lasting 48h for each patient (between starting of the PCA infusion (T0) and the following 48h).

Interventions

morphine chlorhydrate

The drug will be administrated by a bolus 45 minutes before the end of the surgery, with the following modalities: bolus with morphine chlorhydrate 0.15 mg/kg ± 20%. Also acetaminophene 1g and ketoprofen 160 mg (ketorolac 30mg) will be administrated during the operation.

At the exit of the operative compartment patients will have an electronic pump (PCA) for 48h with morphine chlorhydrate to be used in boluses by 1 mg with a lock out of 5 mins, max dose 20 mg in 4 hours.

Moreover, ketoprofen will be prescribed 160 mg x 2 per day (ketorolac 30mg x 2) (in case of allergy acetaminophene 1g x 3 daily).

Postoperative analgesic treatment is lasting 48h for each patient (between starting of the PCA infusion (T0) and the following 48h).

Intervention Type: DRUG

Other Intervention Names

morfina cloridrato

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Massimo Allegri

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Massimo Allegri, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Policlinico San Matteo

Locations

Azienda Ospedaliera San Gerardo

Monza, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 26902643 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28829523 (View on PubMed)

Other Identifiers

PT-SM-07-PCA-Gene

Identifier Type: -

Identifier Source: org_study_id