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
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Condition or disease | Intervention/treatment |
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Anesthesia Surgery | Drug: morphine chlorhydrate |
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 |
Actual Enrollment : | 224 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study. |
Study Start Date : | July 2010 |
Actual Primary Completion Date : | July 2013 |
Actual Study Completion Date : | July 2013 |

Group/Cohort | Intervention/treatment |
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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
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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 |
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
|
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 |
- 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%).
- 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 ]
Biospecimen Retention: Samples With DNA

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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Probability Sample |
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

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): NCT01233752
Italy | |
Azienda Ospedaliera San Gerardo | |
Monza, Italy, 20052 | |
Fondazione IRCCS Policlinico San Matteo | |
Pavia, Italy, 27100 |
Principal Investigator: | Massimo Allegri, MD | IRCCS Policlinico San Matteo |
Responsible Party: | Massimo Allegri, MD, IRCCS Policlinico S. Matteo |
ClinicalTrials.gov Identifier: | NCT01233752 |
Other Study ID Numbers: |
PT-SM-07-PCA-Gene |
First Posted: | November 3, 2010 Key Record Dates |
Last Update Posted: | July 19, 2013 |
Last Verified: | July 2013 |
systemic morphine analgesia pharmacogenetics pharmacokinetics |
Morphine Analgesics, Opioid Narcotics Central Nervous System Depressants |
Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents |