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NCT Number: NCT01233752

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

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.

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Key information

Conditions

Anesthesia Surgery

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Azienda Ospedaliera San Gerardo, Monza, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

morphine chlorhydrate

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).

Other names: morfina cloridrato

Primary outcomes

  1. 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%).

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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").

  5. Detection of the possible side effects.

    Time frame: 72 h postopratively

  6. Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects).

    Time frame: within 72 h postoperatively

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Other

Registry information

Official study title

Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.

Acronym: PCA-Gene

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Nov 3, 2010
Registry last updated
Jul 19, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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