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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

January 13, 2009
December 10, 2012
September 2006
December 2010   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00822549 on ClinicalTrials.gov Archive Site
  • - 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 ]
Same as current
Not Provided
Not Provided
 
Pharmacokinetic, Pharmacodynamic and Pharmacogenetic of Morphine After Surgery
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).

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.

Observational
Time Perspective: Cross-Sectional
Not Provided
Not Provided
Non-Probability Sample

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

Orthopaedic Surgery
Drug: intravenous morphine titration
intravenous morphine titration
Other Name: intravenous morphine titration
1
all the patients included in the study received intravenous morphine in PACU and in the wards
Intervention: Drug: intravenous morphine titration
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
438
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00822549
AOR 05038
No
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: Frederic Aubrun, MD, PhD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP