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Association Between Clinical Effect of Continuous Morphine Administration After Surgery and Pharmacogenetics

This study has been withdrawn prior to enrollment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01233219
First Posted: November 3, 2010
Last Update Posted: March 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Massimo Allegri, IRCCS Policlinico S. Matteo
  Purpose
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.

Condition Intervention
Anesthesia Surgery Drug: morphine chlorhydrate

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Association Between Clinical Effect of Continuous Morphine Administration in Patients After Major Surgery and Pharmacogenetics: Perspective Observational Clinical Study

Resource links provided by NLM:


Further study details as provided by Massimo Allegri, IRCCS Policlinico S. Matteo:

Primary Outcome Measures:
  • Assessment of the rescue doses 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 ]
    Valuation of the rescue doses 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 Outcome Measures:
  • 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.

  • Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure [ Time Frame: period between 24 - 48 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 the period between 24-48 hours postsurgery.

  • Pharmacokinetics of morphine during continuous administration after surgery [ Time Frame: 48 h after surgery ]
    Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).

  • Detection of the possible side effects. [ Time Frame: 72 h postopratively ]
    Detection of the possible side effects after continuous morphine administration

  • Detection of the association between M3G/M6G ratio and polymorphisms of UGTs [ Time Frame: within 72 h postoperatively ]
    Detection of the association between M3G/M6G ratio and polymorphisms of UGTs and its possible side effects.


Biospecimen Retention:   Samples With DNA
genes OPRM1, COMT, UGTs, ESR1

Enrollment: 0
Study Start Date: November 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group A
Homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene
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 continuous infusion for 48h with morphine chlorhydrate 0,02 mg/kg/h.

Moreover, a rescue dose therapy will be prescribed with ketoprofen 160 mg or ketorolac 30mg (in case of allergy acetaminophene 1g) if NRS<4 maximum x 3 daily.

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

Other Name: morfina cloridrato
Group B
Both homozygous and heterozygous patients for the less frequent allele of the polymorphism A118G of OPRM1 gene
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 continuous infusion for 48h with morphine chlorhydrate 0,02 mg/kg/h.

Moreover, a rescue dose therapy will be prescribed with ketoprofen 160 mg or ketorolac 30mg (in case of allergy acetaminophene 1g) if NRS<4 maximum x 3 daily.

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

Other Name: morfina cloridrato

Detailed Description:
Valuation of the rescue doses 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%).
  Eligibility

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Pazients scheduled for major abdominal or urological surgery with postoperative pain control with continuous morphine administration
Criteria

Inclusion criteria:

  • Males and females over 18 years, under 75 years, scheduled for postoperative pain control with continuous 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01233219


Locations
Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
Investigators
Principal Investigator: Massimo Allegri, MD IRCCS Policlinico San Matteo
  More Information

Responsible Party: Massimo Allegri, MD, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT01233219     History of Changes
Other Study ID Numbers: PT-SM-08-MorfinaContinua-Gene
First Submitted: November 2, 2010
First Posted: November 3, 2010
Last Update Posted: March 3, 2017
Last Verified: March 2017

Keywords provided by Massimo Allegri, IRCCS Policlinico S. Matteo:
systemic morphine analgesia
pharmacogenetics
pharmacokinetics

Additional relevant MeSH terms:
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents