Clinical trial NCT00564486: Analgesic Efficacy & Safety of Intravenous (IV) Acetaminophen Versus Placebo for the Treatment of Postop Pain
Official title: Phase 3 Randomized, Double-Blind Placebo-Controlled, Multicenter, Parallel-Group, Repeated-Dose Study of the Analgesic Efficacy & Safety of IV Acetaminophen Versus Placebo for the Treatment of Postop Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Keywords: Abdominal Laparoscopic Surgery
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2007-11-28
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research study will look at the pain relieving ability and safety of using repeated doses of intravenous (into the vein \[IV\]) acetaminophen in the treatment of moderate postoperative pain after planned or elective abdominal laparoscopic surgery, such as a laparoscopic abdominal hysterectomy or laparoscopic cholecystectomy (removal of the gall bladder).

Detailed description: To assess the analgesic efficacy of repeated doses of intravenous acetaminophen (IV APAP) versus Placebo in the treatment of moderate postoperative pain after abdominal laparoscopic surgery.

Eligibility criteria: Inclusion Criteria:

* Provide written Informed Consent prior to participation in the Study
* Is scheduled to undergo abdominal laparoscopic surgery under general anesthesia (laparoscopic bariatric procedures, including gastric bypass or gastric banding, laparoscopic exploratory procedures in which no visceral dissection is performed, and laparoscopic procedures with minimal visceral dissection, such as laparoscopic sterilization,are excluded)
* If Subject is a female of childbearing potential, have a negative pregnancy test within 21 days of surgery
* Be at least 18, but not more than 80 years of age
* Have a Body Mass Index (BMI) ≥ 19 and ≤ 40 lb/in2
* Have an American Society of Anesthesiologist (ASA) risk class of I, II, or III
* Have the ability to read and understand the Study procedures and the use of the pain scales and have the ability to communicate meaningfully with the Study Investigator and staff
* Be free of other physical, mental, or medical conditions which, in the opinion of the Investigator, makes Study participation inadvisable

Exclusion Criteria:

* Used opioids or tramadol daily for greater than 7 days prior to Study Medication administration (Subjects who, in the Investigator's opinion have or are developing opioid tolerance are to be excluded)
* Has been treated with Chapparal, Comfrey, Germander, Gin Bu Huan, Kava, Pennyroyal, Skullcap, St. John's Wort, or Valerian within 14 days prior to surgery
* Has significant medical disease(s), laboratory abnormalities or condition(s) that in the Investigator's judgment could compromise the Subject's welfare, ability to communicate with the Study staff, complete Study activities, or would otherwise contraindicate Study participation
* Has known hypersensitivity to opioids, acetaminophen, or the inactive ingredients (excipients) of the Study Medication
* Has known or suspected history of alcohol or drug abuse or dependence within the previous 2 years
* Has impaired liver function, e.g., aspartate aminotransferase (AST)/Alanine transaminase (ALT)/bilirubin greater than or equal to 3.0 times the upper limit of normal, active hepatic disease, evidence of clinically significant liver disease, or other condition (e.g., alcoholism, cirrhosis, or hepatitis) that may suggest the potential for an increased susceptibility to hepatic toxicity with Study Medication exposure
* Has been treated with monoamine oxidase inhibitors (MAOIs) within 7 days prior to surgery
* Has participated in another clinical Study (investigational or marketed product) within 30 days of surgery

Post Operative Exclusion Criteria

The Subject must not meet any of the following criteria prior to randomization to Study Medication:

* Had any other surgery than the planned laparoscopic surgery or had intra operative or post operative complications which in the view of the Investigator would make Study participation inadvisable
* Has taken non steroidal anti-inflammatory drugs (NSAIDs), steroids or MAOIs during the day after surgery. Exceptions: The use of low-dose aspirin, e.g, 81 mg/day, for cardioprophylaxis, and limited use of topical or inhaled steroids are acceptable.
* Had any neuraxial (spinal or epidural) opioid injected perioperatively
* Had a local anesthetic injection (including into surgical wound at closure) or continuous infusion by any route
* Had an epidural, regional, or percutaneous (intrawound) catheter with continuous local anesthetic infusion used for postoperative analgesic management
* Had a fever (greater than 38.6 ºC or 101.5 ºF) requiring treatment

Post Operative Day 1 Randomization Criterion On the morning of the first post operative day (POD1), the Subject must have a categorical pain intensity score at rest of moderate or severe and a score ≥ 40 mm and ≤ 70 mm at rest on a 100 mm Visual Analogue Scale (VAS)

Primary outcomes:
measure: Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 1 g IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.)
timeFrame: Baseline to 24 hrs
Secondary outcomes:
measure: Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 650 mg IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.)
timeFrame: Baseline to 24 hrs
measure: The Number of Subjects Reporting a Treatment Emergent Adverse Event
timeFrame: First dose through 7 day follow up
measure: The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event
timeFrame: First dose to 30 days after last dose of study medication.
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Phoenix
country: United States
facility: Precision Trials
state: Arizona
city: Arcadia
country: United States
facility: Methodist Hospital
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Laguna Hills
country: United States
facility: Physicians Clinical Research Corporation
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Fort Pierce
country: United States
facility: G and G Research, Inc.
state: Florida
city: Miami
country: United States
facility: Advanced Surgery Associates at Mercy Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Royal Oak
country: United States
facility: William Beaumont Hospital (Royal Oak)
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital (Troy)
state: Michigan
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Houston
country: United States
facility: Memorial Herman/Memorial City Hospital
state: Texas
city: Houston
country: United States
facility: Texas Woman's Hospital
state: Texas
Study officials:
References:
citation: Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB, Singla NK. A randomized, double-blind, placebo-controlled, multicenter, repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clin Ther. 2010 Dec;32(14):2348-69. doi: 10.1016/j.clinthera.2010.12.011.