A Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3 for the Treatment of Pain After Outpatient Surgery

• Sponsor: Nova Scotia Health Authority
• Collaborator: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
• Information provided by: Nova Scotia Health Authority

Study Description

Brief Summary:

Increasingly in general surgery, the investigators are conducting outpatient day surgery. Ambulatory surgery currently comprises 60 to 70% of surgeries performed in North America. These patients all require some form of analgesia which can be taken at home in the first few days after the surgery. The current standard at the investigators' centre and many others in the maritime provinces is to provide a prescription for oral acetaminophen plus codeine or oxycodone (Tylenol #3®, Percocet ®). Some patients may receive more potent opioids such as oral hydromorphone (Dilaudid®). Unfortunately, the most commonly prescribed medication (Tylenol #3®) is often poorly tolerated by patients, has several undesirable side effects, and may not provide effective pain relief. In the investigators' experience, non-steroidal anti-inflammatory drugs (NSAIDs) are uncommonly a routine addition to the home analgesic regimen.

Tylenol #3®, in the investigators' experience and opinion, is a poor post surgical pain medication. They hope to show that a combination of ibuprofen and acetaminophen is better for pain relief after these procedures. The combination of acetaminophen and ibuprofen would be a safe, cheap, and readily available regimen. Unfortunately, as the prescribing practices of surgeons are old habits, it will require a very convincing argument to get them to change their practices. A randomized controlled trial comparing these two regimens, the investigators hope, would be a powerful enough argument.

The hypothesis of this study, therefore, is that the pain control provided by a combination of acetaminophen plus ibuprofen (650 mg/400 mg four times per day) will be superior to Tylenol #3® (600 mg acetaminophen/60 mg codeine/15 mg caffeine four times per day).

This study will attempt to enroll 150 patients in total. Eligible patients will be identified by their attending surgeon and contacted by study personnel. Patients who enroll in the study will undergo their surgery in the usual manner. After the surgery, in the recovery room, once they are ready to go home, they will be randomized to receive combination A or B and be given a week's worth of pain medication. They will then go home and take this medication as directed. They will record their pain intensity and pain relief once per day using a diary provided in the study package. One week after their surgery, they will return to the hospital clinic and be seen by the study nurse. They will hand over the diary and any unused medication. They will also be asked several questions regarding their overall satisfaction, incidence of side effects, and how long until they were pain free.

The risks of participating in this study are minimal from the risks inherent to the procedures and medications the patients would receive within the standard of care. Ibuprofen is a commonly used NSAID which is widely available over the counter and has an established safety profile. The most common adverse effects of ibuprofen and other NSAIDs are gastrointestinal bleeding and ulceration. Other less common adverse effects include nephrotoxicity, hypersensitivity reactions, hepatic dysfunction (longterm use), and cognitive dysfunction. The investigators' patients will be selected to exclude those most at risk for these complications (see exclusion criteria). Acetaminophen has few side effects, with no adverse effects on platelet function and no evidence of gastric irritation.

Condition or disease	Intervention/treatment	Phase
Laparoscopic Cholecystectomy; Inguinal Hernia; Abdominal Hernia; Umbilical Hernia	Drug: Tylenol #3; Drug: Combination Tylenol and Ibuprofen	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double
Primary Purpose:	Treatment
Official Title:	A Randomized Controlled Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3 for the Treatment of Pain After Outpatient Surgery
Study Start Date :	January 2005
Actual Study Completion Date :	December 2005

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Mean daily and final visual analog scale (VAS) scores
2. Mean daily and final Likert scores
3. Total pain relief
4. Sum of pain intensity differences
5. Cumulative weekly VAS scores

Secondary Outcome Measures :

1. Treatment failures
2. Amount of medication used
3. Days to stopping medication
4. Incidence of side effects
5. Compliance with regimen

Eligibility Criteria

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Ages Eligible for Study:	17 Years to 65 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients may take part in this study if the answer is YES to all of these questions:

• Female or male between 17-65 years of age

• Going to have one of the following surgeries:

  • umbilical hernia repair
  • inguinal hernia repair
  • small incisional or abdominal wall hernia repair
  • laparoscopic cholecystectomy (gallbladder removed)
• Going home after their surgery the same day
• Have signed consent form.

Exclusion Criteria:

Patients have had or have:

• Been diagnosed with peptic ulcer disease or bleeding stomach ulcer in the recent past and are not currently on a proton pump inhibitor (special antacid medication, eg. Losec®, Pantoloc®, Prevacid®, Nexium®).
• Suffered from asthma
• Allergies to codeine, non-steroidal anti-inflammatory drugs (Advil®, Ibuprofen), aspirin, or acetaminophen
• Been taking other prescription pain medications prior to their surgery
• A history of chronic pain disorder
• Fibromyalgia (a chronic pain illness with symptoms of muscle aches, pain, stiffness, general fatigue and sleep problems)
• Active kidney disease or failure
• Known liver disease
• Are females who are pregnant or nursing
• A problem with alcohol or drug abuse.

Contacts and Locations

Locations

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Canada, Nova Scotia
Dartmouth General Hospital
Dartmouth, Nova Scotia, Canada, B2Y 4G8

Sponsors and Collaborators

Nova Scotia Health Authority

McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Investigators

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Study Director:	Geoffrey A Porter, MD, FRCSC	CDHA/Dalhousie University

More Information

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ClinicalTrials.gov Identifier:	NCT00245375 History of Changes
Other Study ID Numbers:	CDHA003
First Posted:	October 28, 2005
Last Update Posted:	April 1, 2008
Last Verified:	March 2008

Keywords provided by Nova Scotia Health Authority:

Outpatient Surgery for: inguinal hernia repair; abdominal hernia repair; umbilical hernia repair

Additional relevant MeSH terms:

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Hernia; Hernia, Inguinal; Hernia, Umbilical; Hernia, Abdominal; Pathological Conditions, Anatomical; Infant, Newborn, Diseases; Hernia, Ventral; Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Analgesics	Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action