Multicenter Study to Compare Intravenous and Oral Acetaminophen for the Treatment of Acute Moderate to Severe Pain

A Randomized, Double-Blind, Double-Dummy, Active-Controlled, Repeated Dose, Multicenter Study to Compare Intravenous and Oral Acetaminophen for the Treatment of Acute Moderate to Severe Pain in Combination With Patient-Controlled Analgesia With Morphine in Adults Following Elective Total Knee Arthroplasty

The purpose of this study is to compare intravenous (IV) and oral acetaminophen for the treatment of acute moderate to severe pain in combination with standard patient-controlled analgesia (PCA) in adult subjects following total knee replacement.

Study Overview

• Status: Terminated
• Conditions: Acute Pain, Postoperative
• Intervention / Treatment: Drug: IV acetaminophen; Drug: Morphine; Drug: Oral acetaminophen

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Pensacola, Florida, United States, 32503
      • Pensacola Research Consultants
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University, Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the informed consent form.
2. Subject must be male or females, between 50 and 90 years of age (inclusive) at Screening.
3. Subject must have a weight range of 50 to 120 kg.
4. Subject must be in a American Society of Anesthesiologists risk class of I, II, or III.
5. Subject must have successfully completed an unilateral uncomplicated total knee replacement surgery, able to take oral medication, and report having moderate to severe acute pain as determined by a pain score ≥ 5 from the 11-point Numeric Pain Rating Scale (NPRS) scale during the period of 3 to 6 hours postsurgery.
6. Female subjects of child-bearing potential must have a negative serum pregnancy test at the Screening and day-of-surgery.
7. Subjects must be able to communicate effectively with study personnel.
8. Subject must be able and willing to follow all protocol requirements, including operating a PCA device, and study restrictions.

Exclusion Criteria:

1. Subject is from a vulnerable population, as defined by the Code of Federal Regulations Title 45, Part 46, 1. Section 46.111(b), including but not limited to employees (temporary, part-time, full time, etc.) or a family member of the research staff conducting the study, or of the sponsor, or of the clinical research organization, or of the Institutional Review Board.
2. Subject has an oxygen saturation of less than 95% while awake on room air.
3. Subject has a positive test result for human immunodeficiency virus, hepatitis B (surface antigen), or hepatitis C virus antibody at Screening.
4. Subject has used an average of 30 mg oral morphine equivalents or greater, 1 to 2 weeks prior to the day of surgery. Subjects who, in the investigator's opinion are developing opioid tolerance will be excluded.
5. Subject has a history of any drug allergy, hypersensitivity, or intolerance to acetaminophen or morphine or to any of the excipients in the IV or oral formulations used.
6. Subject has intra- or postoperative complications, which in the view of the investigator, makes the subject unsuitable for the participation of the study.
7. Subject has received neuraxial (spinal or epidural) opioid injected perioperatively.
8. Subject has received a local anesthetic, regional, or wound injection or continuous infusion by any route.
9. Subject has impaired liver function (eg, aspartate aminotransferase, alanine aminotransferase, or 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 (eg, alcoholism, cirrhosis, or hepatitis) that suggests the potential for an increased susceptibility to hepatic toxicity with study drug exposure.
10. Subject has renal dysfunction or is at risk for renal failure due to volume depletion.
11. Subject has donated or had significant loss of whole blood (480 mL or more) within 30 days, or plasma within 14 days prior to dosing.
12. Subject has had any major surgery within 3 months prior to day-of-surgery.
13. Subject has a history of acute illness within 14 days prior to day-of-surgery.
14. Subject has participated in another clinical study within 30 days prior to day-of-surgery or plans to participate in another clinical study while concurrently enrolled in this study.
15. Subject has a history of conditions which might be specifically contraindicated or require caution to be used during the administration of any drug in the study.
16. Subject has any other medical, psychiatric and/or social reason for exclusion as determined by the investigator.
17. Subject has a positive test result for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids [including medical use of marijuana], cocaine, methamphetamine, methadone, or methylenedioxy-methamphetamine) at Screening. Subjects with a positive test result for prescribed drugs may be included in the study at the discretion of the investigator. Subjects with a positive test result for cannabinoids with a prescription for medical marijuana will be excluded from the study, subjects with a prescription for dronabinol (∆-9-tetrahydrocannabinol) may be included at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV acetaminophen/Morphine; IV acetaminophen 1000 mg every 6 hours over 18 hours	Drug: IV acetaminophen; Other Names: Ofirmev; Drug: Morphine; Patient controlled analgesia
Active Comparator: Oral acetaminophen/Morphine; Oral acetaminophen two 500 mg tablets every 6 hours over 18 hours	Drug: Morphine; Patient controlled analgesia; Drug: Oral acetaminophen; Other Names: Acetaminophen (APAP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity on a Numerical Pain Scale (NPS) for 18 Hours	Participants rate intensity of their pain on a Numerical Pain Scale (NPS) from 0-10, wherein 0=no pain (better) and 10=most intense pain (worse). The highest possible score is 10.	18 hours

Collaborators and Investigators

• Sponsor: Mallinckrodt
• Investigators: Study Director: Medical Affairs, Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2016
• Primary Completion (Actual): May 5, 2016
• Study Completion (Actual): May 5, 2016

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 21, 2016

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Elective total knee arthroplasty
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Morphine
• Other Study ID Numbers: MNK14504054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No