Pharmacokinetic, Pharmacodynamic and Pharmacogenetic of Morphine After Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00822549
First received: January 13, 2009
Last updated: December 10, 2012
Last verified: January 2009
  Purpose

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).


Condition Intervention
Orthopaedic Surgery
Drug: intravenous morphine titration

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Assessment of the Pharmacokinetic, Pharmacodynamic, Pharmacogenetic Relationships of Morphine and Metabolites After Severe Postoperative Pain in Adults

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • To improve our knowledge on the pharmacodynamic, pharmacokinetic and pharmacogenetic relationships of morphine administered after severe postoperative pain. [ Time Frame: during the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • - 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) ] [ Designated as safety issue: No ]
  • - Relationships between clinical events (pain relief, failure in pain relief, adverse effects) and genetic polymorphism. [ Time Frame: Immediate postoperative period (PACU) ] [ Designated as safety issue: No ]
  • - 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 ] [ Designated as safety issue: No ]
  • To better characterize the age- and sex-related differences which differ between acute and sub-acute periods. [ Time Frame: during the study ] [ Designated as safety issue: No ]

Enrollment: 438
Study Start Date: September 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
all the patients included in the study received intravenous morphine in PACU and in the wards
Drug: intravenous morphine titration
intravenous morphine titration
Other Name: intravenous morphine titration

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00822549

Locations
France
Hopital de la Pitié Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Frederic Aubrun, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00822549     History of Changes
Other Study ID Numbers: AOR 05038
Study First Received: January 13, 2009
Last Updated: December 10, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Morphine titration
Sub acute pain
Major orthopaedic surgery
Pharmacokinetics
Pharmacodynamics
Genetic polymorphism
PACU
Patients undergoing major scheduled orthopaedic surgery

Additional relevant MeSH terms:
Morphine
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotics

ClinicalTrials.gov processed this record on April 23, 2014