Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients

• ClinicalTrials.gov Identifier: NCT00598559
• Recruitment Status: Completed
• First Posted: January 22, 2008
• Results First Posted: December 10, 2010
• Last Update Posted: October 21, 2016
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

Tracking Information

• First Submitted Date: January 8, 2008
• First Posted Date: January 22, 2008
• Results First Submitted Date: September 25, 2009
• Results First Posted Date: December 10, 2010
• Last Update Posted Date: October 21, 2016
• Study Start Date: January 2008
• Actual Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2015)

• Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). [ Time Frame: T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up ]
  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).
• Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) [ Time Frame: First dose (T0) to within 30 days of the last dose of study medication. ]
  Serious TEAE is any untoward medical occurrences at any dose of 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

• Original Primary Outcome Measures (submitted: January 21, 2008): Spontaneous SAE Reports. [ Time Frame: 5 days ]
• Change History: Complete list of historical versions of study NCT00598559 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 11, 2010)

• Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments [ Time Frame: End of Day 5 (prior to discharge) ]
  Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with side effects related to study treatment at End of Day 5 (prior to discharge)
• Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. [ Time Frame: Study period lookback at Day 7 ]
  Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with study treatments looking back over the entire treatment period was conducted at Day 7.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients
• Official Title: A Phase III, Multi-Center, Open-Label, Prospective, Repeated Dose, Randomized, Controlled, Multi-Day Study of the Safety and Efficacy of Intravenous Acetaminophen in Adult Inpatients
• Brief Summary: The study will be investigating safety and efficacy administration of repeated dose of IV Acetaminophen (IV APAP) over five days for the treatment of acute pain or fever in adult patients.

Detailed Description

• To assess the safety of IV Acetaminophen when used over five days for the treatment of acute pain or fever in adult inpatients

Secondary Objectives:

• To compare the efficacy of IV Acetaminophen 650 milligram (mg) every four (q4) hours vs. 1 gram (g) every 6 (q6) hours over 5 days of treatment
• To compare the safety of IV Acetaminophen 650 mg q4 hours vs. 1 g q6 hours over 5 days of treatment
• To compare the safety of IV Acetaminophen vs. standard of care (SOC) treatment over 5 days of treatment
• To compare the efficacy of IV Acetaminophen vs. standard of care treatment over 5 days of treatment

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Pain
• Fever

Intervention

Drug: IV Acetaminophen

Arm 1: 1 g IV Acetaminophen every 6 hours administered for five days. Arm 2: 650 mg IV Acetaminophen every 4 hours administered for five days. Arm 3: The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen.

Other Name: IV Acetaminophen (IV APAP)

Study Arms

• Experimental: 1 g IV Acetaminophen
  1 g q6h IV Acetaminophen
  Intervention: Drug: IV Acetaminophen
• Experimental: 650 mg IV Acetaminophen
  650 mg q4h IV Acetaminophen
  Intervention: Drug: IV Acetaminophen
• Standard of Care
  The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen.
  Intervention: Drug: IV Acetaminophen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 11, 2010): 213
• Original Estimated Enrollment (submitted: January 21, 2008): 175
• Actual Study Completion Date: November 2008
• Actual Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Provide written informed consent prior to participation in the Study
• Be at least 18 years of age and weigh at least 41 kilogram (kg)
• Be anticipated by the Investigator to require multi-day (target is five days) use of IV treatment either because of having a "nothing by mouth" (NPO) status having a medical condition that makes oral intake difficult having a medical condition that requires IV treatment
• Be willing to undergo 5 days of treatment with IV acetaminophen for the treatment of pain or fever (defined as a core temperature greater than or equal to 38 degrees celsius). Note that Subjects have a slightly less than 15% chance (one in seven) of being assigned to the Control Group and receiving standard of care treatment, but no IV APAP.
• Have the ability to read and understand the Study procedures and have the ability to communicate meaningfully with the Study Investigator and staff
• If a female of child bearing potential, have a negative pregnancy test within 48 hours of randomization

Exclusion Criteria:

• Has a significant medical disease, laboratory abnormality or condition that, in the Investigator's judgment, could compromise the Subject's welfare or would otherwise contraindicate Study participation
• Is expected to have difficulty in communicating with the Study staff or completing Study requirements (including follow up visits)
• Has known hypersensitivity to acetaminophen or the inactive ingredients (excipients) of IV acetaminophen or any contraindication to receiving acetaminophen
• Has impaired liver function, e.g., Alanine aminotransferase (ALT) greater than or equal to 3 times the upper limit of normal (ULN), bilirubin greater than or equal to 3 times ULN, known active hepatic disease (e.g., hepatitis), evidence of clinically significant chronic liver disease or other condition affecting the liver (e.g., alcoholism as defined by DSM-IV, cirrhosis or chronic hepatitis)
• Has participated in an interventional clinical Study (investigational or marketed product) within 30 days of Study entry

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00598559
• Other Study ID Numbers: CPI-APA-351
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mallinckrodt
• Study Sponsor: Mallinckrodt
• Collaborators: Not Provided

Investigators

• Principal Investigator: Eugene Viscusi, MD; Thomas Jefferson University

• PRS Account: Mallinckrodt
• Verification Date: September 2016