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

Surgery Clinical Trial

Official title:

Association Between Clinical Effect of Continuous Morphine Administration in Patients After Major Surgery and Pharmacogenetics: Perspective Observational Clinical Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01233219
• Other study ID #: PT-SM-08-MorfinaContinua-Gene
• Status: Withdrawn
• Phase: N/A
• First received: November 2, 2010
• Last updated: March 1, 2017
• Start date: November 2010
• Est. completion date: November 2013

Study information

• Verified date: March 2017
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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%).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• 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 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).

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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%).	first 24 h after surgery
Secondary	Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure	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.	during 24 h postsurgery
Secondary	Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure	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.	period between 24 - 48 h postsurgery
Secondary	Pharmacokinetics of morphine during continuous administration after surgery	Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).	48 h after surgery
Secondary	Detection of the possible side effects.	Detection of the possible side effects after continuous morphine administration	72 h postopratively
Secondary	Detection of the association between M3G/M6G ratio and polymorphisms of UGTs	Detection of the association between M3G/M6G ratio and polymorphisms of UGTs and its possible side effects.	within 72 h postoperatively