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

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ClinicalTrials.gov Identifier: NCT01233752
Recruitment Status : Completed
First Posted : November 3, 2010
Last Update Posted : July 19, 2013
Sponsor:
Information provided by (Responsible Party):
Massimo Allegri, IRCCS Policlinico S. Matteo

Tracking Information
First Submitted Date November 2, 2010
First Posted Date November 3, 2010
Last Update Posted Date July 19, 2013
Study Start Date July 2010
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 2, 2010)
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%).
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 2, 2010)
  • Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure [ Time Frame: 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.
  • Detection of the medium morphine dose [ Time Frame: 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.
  • Pharmacokinetics of morphine with PCA after surgery [ Time Frame: 48 h after surgery ]
    Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).
  • Variants frequency at loci OPRM1, COMT, UGTs, ESR1 [ Time Frame: 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 possible side effects. [ Time Frame: 72 h postopratively ]
  • Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects). [ Time Frame: within 72 h postoperatively ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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.
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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
genes OPRM1, COMT, UGTs, ESR1
Sampling Method Probability Sample
Study Population Pazients scheduled for major abdominal or urological surgery with postoperative pain control by PCA morphine administration
Condition
  • Anesthesia
  • Surgery
Intervention Drug: 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).

Other Name: morfina cloridrato
Study Groups/Cohorts
  • 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: Drug: 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: Drug: morphine chlorhydrate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 18, 2013)
224
Original Estimated Enrollment
 (submitted: November 2, 2010)
0
Actual Study Completion Date July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT01233752
Other Study ID Numbers PT-SM-07-PCA-Gene
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Massimo Allegri, IRCCS Policlinico S. Matteo
Study Sponsor IRCCS Policlinico S. Matteo
Collaborators Not Provided
Investigators
Principal Investigator: Massimo Allegri, MD IRCCS Policlinico San Matteo
PRS Account IRCCS Policlinico S. Matteo
Verification Date July 2013