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

NCT01233219 | Withdrawn DMC

• 1 other identifier: PT-SM-08-MorfinaContinua-Gene
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Anesthesia; Surgery

Keywords

systemic morphine analgesia; pharmacogenetics; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure

  during 24 h postsurgery

• Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure

  period between 24 - 48 h postsurgery

• Pharmacokinetics of morphine during continuous administration after surgery

  48 h after surgery

• Detection of the possible side effects.

  72 h postopratively

• Detection of the association between M3G/M6G ratio and polymorphisms of UGTs

  within 72 h postoperatively

Study Arms (2)

Group A

Homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene

Drug: morphine chlorhydrate

Group B

Both homozygous and heterozygous patients for the less frequent allele of the polymorphism A118G of OPRM1 gene

Drug: morphine chlorhydrate

Interventions

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 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).

Also known as: morfina cloridrato

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Pazients scheduled for major abdominal or urological surgery with postoperative pain control with continuous morphine administration

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

genes OPRM1, COMT, UGTs, ESR1

Study Officials

• Massimo Allegri, MD

  IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 3, 2010
• Study Start: November 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

IT (1)