Official Title: “A Randomized Controlled Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3® for the Treatment of Pain After Breast Surgery.”

Current standard of care for post-operative analgesia after breast surgery in CDHA is Tylenol #3® (300 mg acetaminophen, 30 mg codeine, 15 mg caffeine per tablet). We are proposing to test the analgesic efficacy of acetaminophen plus ibuprofen against Tylenol #3® in patients undergoing outpatient breast surgery.

Study Type: Interventional

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

Study Primary Completion Date: May 2008

Block randomization will be used to randomize patients to one of two combinations. Group A will receive capsules containing 650 mg Acetaminophen plus 400 mg Ibuprofen. Group B will receive capsules containing 600 mg Acetaminophen, 15 mg caffeine and 60 mg codeine. Capsules are placed in identical dossettes containing a seven day supply. Patients are instructed to start taking their medications post-op and continue until they are pain free. All participants are given a series of blank Visual Analogue scales and Likert scales and instructed to record their level of pain intensity and pain relief four times per day for the entire week. Peri-operative pain management will be standardized. Patients will not receive pre-operative analgesics. Intra-operative analgesia will be intravenous opioids as selected by anaesthesiology. No local/regional anaesthesia will be used. Intravenous ketorolac will not be allowed for trial participants. All patients will receive intravenous opioid and anti-emetic if required in PACU. Any patients with peri-operative complications or other problems requiring admission or alternative analgesics will be excluded.

Intervention(s) in this Clinical Trial

• Drug: acetaminophen plus codeine
  • capsules four times daily until pain free or for a maximum of seven days
• Drug: acetaminophen plus ibuprofen
  • capsules four times daily until pain free or for a maximum of seven days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Active Comparator: 2

Primary Measures

• VAS Scores.
  • Time Frame: mean and daily
    Safety Issue?: No
• maximum VAS scores.
  • Time Frame: daily
    Safety Issue?: No
• Likert scores.
  • Time Frame: mean daily and final
    Safety Issue?: No
• Patient satisfaction with analgesic regimen.
  • Time Frame: day 7
    Safety Issue?: No
• Treatment failures-inadequate pain relief or inability to tolerate side effects.
  • Time Frame: daily
    Safety Issue?: No
• Time to stopping medication.
  • Time Frame: day 7
    Safety Issue?: No

Secondary Measures

• Total Pain relief (TOTPAR).
  • Time Frame: daily
    Safety Issue?: No
• Sum of pain intensity differences (SPID).
  • Time Frame: day7
    Safety Issue?: No
• Amount of medication used.
  • Time Frame: day 7
    Safety Issue?: No
• Incidence of side effects.
  • Time Frame: day 7
    Safety Issue?: No
• Compliance with regimen.
  • Time Frame: day 7
    Safety Issue?: No

Inclusion Criteria:

• ages 18 to 70 inclusive
• outpatient breast surgery: lumpectomy; mastectomy, simple or modified; with or without sentinel lymph node biopsy, axillary node dissection.

Exclusion Criteria:

• allergies to acetaminophen, NSAIDs, ASA or codeine.
• asthma.
• recent reported history of upper GI bleeding.
• daily analgesic use (OTC or opioid) pre-operatively.
• any opioid use in the week prior to surgery.
• reported history of PUD if not on PPI regularly.
• anticoagulant use (low dose ASA excepted).
• renal disease or impairment.
• reported history of liver disease.
• pregnancy.
• major operative complications.
• patients requiring admission.
• communication barrier.
• cognitive or memory impairment.
• reported history of drug and/or alcohol abuse.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Capital District Health Authority, Canada

Overall Clinical Trial Officials and Contacts

Alex D Mitchell, MD Principal Investigator CDHA, Dalhousie University  

Overall Contact: Alex D Mitchell, MD 430-5995 admitche@dal.ca

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00299039

Study ID Number: CDHA008

ClinicalTrials.gov Identifier: NCT00299039

Health Authority: Canada: Health Canada