Pharmacokinetic, Pharmacodynamic and Pharmacogenetic of Morphine After Surgery

December 10, 2012 updated by: Assistance Publique - Hôpitaux de Paris

Assessment of the Pharmacokinetic, Pharmacodynamic, Pharmacogenetic Relationships of Morphine and Metabolites After Severe Postoperative Pain in Adults

The main objective of this study is to improve our knowledge on the pharmacodynamic, pharmacokinetic, and pharmacogenetic relationships of morphine administered to relief severe postoperative pain. The analysis will encompass the efficacy (acute during titration and subacute during the first 24 hours) and adverse effects of morphine. Our purpose is also to better characterize the age- and sex-related differences which probably markedly differ between the two periods (acute vs sub acute).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

No previous study attempted to characterize the pharmacodynamic, pharmacokinetic, and pharmacogenetic relationships of morphine in the early postoperative period, whereas it is the main clinical situation for severe pain and a unique model for its study (not possible in the healthy volunteer). Indeed, intravenous titration of morphine is the first step for pain control in the postanesthesia care unit. Administration of intravenous boluses of morphine enables to obtain complete pain relief in 98% of the patients. We intend to study the effects of morphine (intravenous titration then patient-controlled intravenous administration (PCA) for 24 hours), perform dosages of plasma concentration of morphine an its main metabolites, and also study gene polymorphisms coding for main proteins involved in the pharmacokinetic and pharmacodynamic profile of morphine (hepatic metabolism, distribution and elimination, interaction with morphine receptor). Five hundred patients scheduled for major orthopedic surgery will be included in this prospective study. The main objective of this study is to improve our knowledge on the pharmacodynamic, pharmacokinetic, and pharmacogenetic relationships of morphine administered to relief severe postoperative pain. The analysis will encompass the efficacy (acute during titration and subacute during the first 24 hours) and adverse effects of morphine. Our purpose is also to better characterize the age- and sex-related differences which probably markedly differ between the two periods (acute vs subacute). We consider that this knowledge is important to confirm or not several important concepts currently used to define the appropriate analgesic regimen to control severe pain in the postoperative period.

Study Type

Observational

Enrollment (Actual)

438

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Hôpital de la Pitié Salpêtrière

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients undergoing major orthopaedic surgery with severe postoperative pain. All the patients included in the study received intravenous morphine

Description

Inclusion criteria :

  • scheduled major orthopedic surgery
  • spine, hip or knee surgery
  • Body weight between 50 and 100 kg
  • Caucasians
  • ASA status 1 to 3
  • no cognitive dysfunction

Exclusion criteria :

  • allergy or contraindication to morphine
  • renal impairment (Cr Cl < 30 ml/min)
  • severe hepatic impairment
  • surgery performed under regional anaesthesia
  • preoperative treatment including strong or weak opioids
  • pregnancy, patients under 18 years, addiction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
all the patients included in the study received intravenous morphine in PACU and in the wards
Drug: intravenous morphine titration
intravenous morphine titration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To improve our knowledge on the pharmacodynamic, pharmacokinetic and pharmacogenetic relationships of morphine administered after severe postoperative pain.
Time Frame: during the study
during the study

Secondary Outcome Measures

Outcome Measure
Time Frame
- Relationships between morphine consumption, clinical events (efficacy or adverse effects) and morphine (and metabolites) blood concentrations. Immediate postoperative period (PACU)
Time Frame: Immediate postoperative period (PACU)
Immediate postoperative period (PACU)
- Relationships between clinical events (pain relief, failure in pain relief, adverse effects) and genetic polymorphism.
Time Frame: Immediate postoperative period (PACU)
Immediate postoperative period (PACU)
- Relationships between sub-acute clinical events and PK/PG profile. (on the wards at 24 hours after surgery)
Time Frame: on the wards at 24 hours after surgery
on the wards at 24 hours after surgery
To better characterize the age- and sex-related differences which differ between acute and sub-acute periods.
Time Frame: during the study
during the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Frederic Aubrun, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

January 13, 2009

First Submitted That Met QC Criteria

January 13, 2009

First Posted (Estimate)

January 14, 2009

Study Record Updates

Last Update Posted (Estimate)

December 11, 2012

Last Update Submitted That Met QC Criteria

December 10, 2012

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOR 05038

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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