Pharmacokinetic, Pharmacodynamic and Pharmacogenetic of Morphine After Surgery

Orthopaedic Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00822549
• Other study ID #: AOR 05038
• Status: Completed
• Phase: N/A
• First received: January 13, 2009
• Last updated: December 10, 2012
• Start date: September 2006
• Est. completion date: December 2010

Study information

• Verified date: January 2009
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 438
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Orthopaedic Surgery

Intervention

Drug:
• intravenous morphine titration
intravenous morphine titration

Locations

Country	Name	City	State
France	Hopital de la Pitié Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To improve our knowledge on the pharmacodynamic, pharmacokinetic and pharmacogenetic relationships of morphine administered after severe postoperative pain.		during the study	No
Secondary	- Relationships between morphine consumption, clinical events (efficacy or adverse effects) and morphine (and metabolites) blood concentrations. Immediate postoperative period (PACU)		Immediate postoperative period (PACU)	No
Secondary	- Relationships between clinical events (pain relief, failure in pain relief, adverse effects) and genetic polymorphism.		Immediate postoperative period (PACU)	No
Secondary	- Relationships between sub-acute clinical events and PK/PG profile. (on the wards at 24 hours after surgery)		on the wards at 24 hours after surgery	No
Secondary	To better characterize the age- and sex-related differences which differ between acute and sub-acute periods.		during the study	No