Analgesic Efficacy & Safety of Intravenous (IV) Acetaminophen Versus Placebo for the Treatment of Postop Pain

Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00564486
• Other study ID #: CPI-APA-304
• Status: Completed
• Phase: Phase 3
• First received: November 26, 2007
• Last updated: May 14, 2015
• Start date: November 2007
• Est. completion date: September 2008

Study information

• Verified date: May 2015
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• IV Placebo
IV, every 6 hours for 24 hours (4 doses total)
• IV Placebo
IV, every 4 hours for 24 hours (6 doses total)
• IV Acetaminophen
IV, every 6 hours for 24 hours (4 doses total)
• IV Acetaminophen
IV, every 4 hours for 24 hours (6 doses total)

Locations

Country	Name	City	State
United States	Methodist Hospital	Arcadia	California
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Cooper University Hospital	Camden	New Jersey
United States	Nature Coast Clinical Research	Crystal River	Florida
United States	G and G Research, Inc.	Fort Pierce	Florida
United States	Glendale Adventist Medical Center	Glendale	California
United States	Memorial Herman/Memorial City Hospital	Houston	Texas
United States	Texas Woman's Hospital	Houston	Texas
United States	Physicians Clinical Research Corporation	Laguna Hills	California
United States	Advanced Surgery Associates at Mercy Hospital	Miami	Florida
United States	University of Miami School of Medicine	Miami	Florida
United States	Huntington Memorial Hospital	Pasadena	California
United States	Precision Trials	Phoenix	Arizona
United States	William Beaumont Hospital (Royal Oak)	Royal Oak	Michigan
United States	William Beaumont Hospital (Troy)	Royal Oak	Michigan
United States	Helen Keller Hospital	Sheffield	Alabama
United States	Staten Island University Hospital	Staten Island	New York

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)	Pain Intensity (PI) as measured by a 100 millimeter (mm) long Visual Analogue Scale (VAS) over 24 hours after treatment minus the Baseline VAS score. The 100 mm VAS was drawn on a pain ruler and labeled at its left end with '0 = No Pain' and with "100 = Worst Pain Imaginable' at its right end. Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI at baseline was compared to the PI at each timepoint and differences were summed over the 24 hour time period.	Baseline to 24 hrs	No
Secondary	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.)	Sum of Pain Intensity (PI) as measured by the 100 mm long Visual Analogue Scale (VAS) over 24 hours after treatment subtracting the Baseline VAS score.The 100 mm VAS was drawn on a pain ruler and labeled at it's left end with "0 = No Pain' and its right end with '100 = Worst Pain Imaginable.' Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI difference from baseline was calculated at each assessment over a 24 hour period.	Baseline to 24 hrs	No
Secondary	The Number of Subjects Reporting a Treatment Emergent Adverse Event	Number of subjects who experienced at least one treatment emergent adverse event (TEAE).; A TEAE is an adverse event that occurs on or after the first dose of study medication (T0).	First dose through 7 day follow up	Yes
Secondary	The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event	The number of subjects who reported at least one treatment emergent SAE during the study.; A Serious Adverse Event is defined as any untoward medical occurrence at any dose of blinded study medication that: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event	First dose to 30 days after last dose of study medication.	Yes