Official Title: “The Effect of the Combined Use of Naloxone and Tramacet on Postoperative Analgesia in Elderly Patients Having Joint Replacement Surgery: a Randomized Controlled Study.”

Patients over 70 years of age, scheduled for joint replacement surgery will be randomized to tramacet/ naloxone plus morphine PCA or to morphine PCA to assess quality of analgesia in the postoperative period.

The primary objective is to determine opioid use during combined use of oral tramacet and naloxone infusion perioperatively in elderly patients (70 yrs and older) having elective knee/ hip arthroplasty under spinal anesthesia.

Secondary objectives are to determine the incidence VAS scores ≥4 and adverse effects such as nausea, vomiting, sedation, respiratory depression, pruritus, confusion, and time of independent mobilization.

Hypothesis: Perioperative naloxone infusion and tramacet provides adequate analgesia in elderly patients undergoing total knee/hip arthroplasty and is associated with 80% reduction in opioid use and reduced opioid-induced side effects.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment

Study Primary Completion Date: November 2008

Intervention(s) in this Clinical Trial

• Drug: tramacet, naloxone
  • Group A: oral tramacet 2 tablets preoperatively, then 2 tablets every 6 hours for 5 days then 1-2 tablets of tramacet prn to a maximum of 8 tablets per day. A naloxone infusion will started preop at 0.25ug/kg/hr and will continue during patient's stay in hospital (an equivalent of 400ug over 24 hours in a 70 kg man). Infusion discontinued 1 hour before patient discharge. All the patients in groups A and B will be provided Morphine PCA for the duration of their hospital stay. Use of morphine PCA will be noted.Oral celebrex 200mg will be given to all the patient twice a day for five days as per our standard practice. All patients will receive peri-articular infiltration with local anesthetic solution intraoperatively by the surgeon as per our standard practice.
• Drug: tramacet
  • Group B: oral tramacet 2 tablets preop,then 2 tablets every 6 hours for five days(or until discharge. Patient VAS after discontinuation of morphine PCA may dictate addition of oral narcotic oxycodone after discharge). Group also receives saline infusion at 4-6mls/hour during hospital stay.All patients in groups A and B will have Morphine PCA during hospital stay. Use of morphine PCA will be noted. Oral celebrex 200mg will be given to all the patient twice a day for five days as per our standard practice. All patients will receive peri-articular infiltration with local anesthetic solution intraopby the surgeon as per our standard practice.
• Drug: Acetaminophen
  • Group C will receive oral Acetaminophen tablets 1 gm preoperatively and subsequently 6 hourly plus an infusion of saline (placebo) at a rate of 4-6mls / hour for the duration of their stay. Oral celebrex 200mg will be given to all the patient twice a day for five days as per our standard practice. All patients will receive peri-articular infiltration with local anesthetic solution intraoperatively by the surgeon as per our standard practice. The Visual Analogue Scale, the Ramsay Sedation Score and the Mini Mental State Exam will be used to assess the patients for pain, sedation and confusion every 6 hours while in hospital.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Group A oral tramacet 2 tablets preoperatively, 2 tablets every 6 hours for 5 days then 1-2 tablets of tramacet prn to a maximum of 8 tablets per day. Naloxone infusion starting preop at 0.25ug/kg/hr and continuing during hospital stay (an equivalent of 400ug over 24 hours in a 70 kg man). The infusion will be discontinued 1 hour before patient discharge.
• Active Comparator: 2
  • Group B will receive oral tramacet 2 tablets preoperatively and then 2 tablets every 6 hours for five days. ( or until discharge. Patient VAS after discontinuation of morphine PCA may dictate addition of oral narcotic oxycodone after discharge). This group will also receive saline infusion at 4-6mls / hour for the duration of the hospital stay.
• Active Comparator: 3
  • Group C will receive oral Acetaminophen tablets 1 gm preoperatively and subsequently 6 hourly plus an infusion of saline (placebo) at a rate of 4-6mls / hour for the duration of their stay.

Primary Measures

• Morphine use / day
  • Time Frame: per day
    Safety Issue?: No

Inclusion Criteria:

• 1. Aged 70 years and older*
• 2. Able to give informed consent
• 3. Able to communicate in English
• 4. Having elective hip/knee arthroplasty
• 5. ASA physical status 1-3.

Exclusion Criteria:

• 1. Allergies to any of the following: naloxone, tramacet, NSAIDs, or local anesthetic
• 2. Contraindication to spinal anesthesia
• 3. Contraindication to use of tramacet or celebrex
• 4. ASA physical status 4
• 5. Chronic opioid use
• 6. Chronic pain syndrome All the above will be included in the letter of information

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 70 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Lawson Health Research Institute

Overall Clinical Trial Officials and Contacts

Overall Contact: Ngozi Imasogie, MBBS, FRCA 519-646-6000 Ngozi.Imasogie@sjhc.london.on.ca

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00679614

Study ID Number: R-07-427

ClinicalTrials.gov Identifier: NCT00679614

Health Authority: Canada: Health Canada