AnesthesiaPCA-GeneNCT01233752
Association Between Clinical Effect of Morphine With PCA After Surgery and Pharmacogenetics
An observational study of Anesthesia and Surgery, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 2 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Anesthesia, Surgery
- What is being tested?
- morphine chlorhydrate
- Type of treatment
- Injection or infusion
- How many people
- 224 participants
- Where
- 2 sitesItaly
- Study dates
- Jul 2010to Jul 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Pazients scheduled for major abdominal or urological surgery with postoperative pain control by PCA morphine administration
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Azienda Ospedaliera San Gerardo
Monza, 20052
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
About this study
Official title: Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.
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.
Read the detailed description
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.
- Conditions
- Anesthesia, Surgery
- Being tested
- morphine chlorhydrate
- Keywords
- systemic morphine analgesia, pharmacogenetics, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
morphine chlorhydrateDrug
Also called morfina cloridrato
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: morphine chlorhydrate | |
| 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 Receives: Drug: morphine chlorhydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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%).
Measured: first 24 h after surgery
Secondary outcomes (6)
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.
Measured: during 24 h postsurgery
Detection of the medium morphine dose
Detection of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 though the first 48 hours after surgery.
Measured: First 24 h after surgery
Pharmacokinetics of morphine with PCA after surgery
Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).
Measured: 48 h after surgery
Variants frequency at loci OPRM1, COMT, UGTs, ESR1
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").
Measured: Within 48h after surgery
Detection of the possible side effects.
Measured: 72 h postopratively
Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects).
Measured: within 72 h postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startJul 2010
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Massimo Allegri, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Massimo Allegri, MD, Principal investigator, IRCCS Policlinico San Matteo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233752
- Sponsor's protocol ID
- PT-SM-07-PCA-Gene
- Acronym
- PCA-Gene
- Status last verified
- Jul 2013
- First submitted
- 2 Nov 2010
- Last updated
- 19 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cattaneo S, Ingelmo P, Scudeller L, Gregori M, Bugada D, Baciarello M, Marchesini M, Alberio G, Normanno M, Jotti GS, Meschi T, Fanelli G, Massimo A. Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery. J Opioid Manag. 2017 Mar/Apr;13(2):85-94. doi: 10.5055/jom.2017.0372.
PubMed 28829523De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, Molinaro V, Garbin G, Ranzani GN, Alberio G, Normanno M, Lovisari F, Somaini M, Govoni S, Mura E, Bugada D, Niebel T, Zorzetto M, De Gregori S, Molinaro M, Fanelli G, Allegri M. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628-36. doi: 10.1016/j.jpain.2016.02.003. Epub 2016 Feb 21.
PubMed 26902643
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Clinical Effect of Morphine in Patients With PCA After Major Surgery and Pharmacogenetics: Prospective Observational Clinical Study.
- ClinicalTrials.gov ID
- NCT01233752
- Acronym / sponsor ID
- PCA-Gene / PT-SM-07-PCA-Gene
- Conditions
- Anesthesia, Surgery
- Keywords
- systemic morphine analgesia, pharmacogenetics, pharmacokinetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 3 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Drug: morphine chlorhydrateHomozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the more frequent allele of the polymorphism A118G of OPRM1 gene |
| Group B | – | Drug: morphine chlorhydrateBoth 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pazients scheduled for major abdominal or urological surgery with postoperative pain control by PCA morphine administration
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| morphine chlorhydrateAlso: morfina cloridratoThe 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). | Drug | Group A, Group B |
Primary outcome
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%).
6 secondary outcomes
Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure
Time frame: during 24 h postsurgery
Detection of the medium morphine dose
Time frame: First 24 h after surgery
Pharmacokinetics of morphine with PCA after surgery
Time frame: 48 h after surgery
Variants frequency at loci OPRM1, COMT, UGTs, ESR1
Time frame: Within 48h after surgery
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2013.
- Derived from this study: PubMed 28829523Cattaneo S, Ingelmo P, Scudeller L, Gregori M, Bugada D, Baciarello M, Marchesini M, Alberio G, Normanno M, Jotti GS, Meschi T, Fanelli G, Massimo A. Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery. J Opioid Manag. 2017 Mar/Apr;13(2):85-94. doi: 10.5055/jom.2017.0372.
- Derived from this study: PubMed 26902643De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, Molinaro V, Garbin G, Ranzani GN, Alberio G, Normanno M, Lovisari F, Somaini M, Govoni S, Mura E, Bugada D, Niebel T, Zorzetto M, De Gregori S, Molinaro M, Fanelli G, Allegri M. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628-36. doi: 10.1016/j.jpain.2016.02.003. Epub 2016 Feb 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Massimo Allegri, MD principal investigator
IRCCS Policlinico San Matteo
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anesthesia and Surgery, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01233752, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2013.