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

NCT02746263 | Terminated Phase 4 Results

• 1 other identifier: MNK14504054
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Acute Pain, Postoperative

Keywords

Elective total knee arthroplasty

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

IV acetaminophen/Morphine

EXPERIMENTAL

IV acetaminophen 1000 mg every 6 hours over 18 hours

Drug: IV acetaminophen; Drug: Morphine

Oral acetaminophen/Morphine

ACTIVE COMPARATOR

Oral acetaminophen two 500 mg tablets every 6 hours over 18 hours

Drug: Oral acetaminophen; Drug: Morphine

Interventions

IV acetaminophen DRUG

Also known as: Ofirmev

IV acetaminophen/Morphine

Oral acetaminophen DRUG

Also known as: Acetaminophen (APAP)

Oral acetaminophen/Morphine

Morphine DRUG

Patient controlled analgesia

IV acetaminophen/Morphine; Oral acetaminophen/Morphine

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject must be male or females, between 50 and 90 years of age (inclusive) at Screening.
• Subject must have a weight range of 50 to 120 kg.
• Subject must be in a American Society of Anesthesiologists risk class of I, II, or III.
• 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.
• Female subjects of child-bearing potential must have a negative serum pregnancy test at the Screening and day-of-surgery.
• Subjects must be able to communicate effectively with study personnel.
• Subject must be able and willing to follow all protocol requirements, including operating a PCA device, and study restrictions.

You may not qualify if:

• 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.
• Subject has an oxygen saturation of less than 95% while awake on room air.
• Subject has a positive test result for human immunodeficiency virus, hepatitis B (surface antigen), or hepatitis C virus antibody at Screening.
• 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.
• 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.
• Subject has intra- or postoperative complications, which in the view of the investigator, makes the subject unsuitable for the participation of the study.
• Subject has received neuraxial (spinal or epidural) opioid injected perioperatively.
• Subject has received a local anesthetic, regional, or wound injection or continuous infusion by any route.
• 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.
• Subject has renal dysfunction or is at risk for renal failure due to volume depletion.
• 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.
• Subject has had any major surgery within 3 months prior to day-of-surgery.
• Subject has a history of acute illness within 14 days prior to day-of-surgery.
• 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.
• 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.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (2)

Pensacola Research Consultants

Pensacola, Florida, 32503, United States

Location

The Ohio State University, Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Acetaminophen; Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

Early termination leading to small number of participants analyzed. The single participant enrolled was in violation of the protocol, leading to unreliable or uninterpretable data. All AEs were listed, but not related to the study drug.

Results Point of Contact

• Title: Medical Information Call Center
• Organization: Mallinckrodt Pharmaceuticals

clinicaltrials@mnk.com

800-556-3314

Study Officials

• Medical Affairs

  Mallinckrodt

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: April 21, 2016
• Study Start: April 27, 2016
• Primary Completion: May 5, 2016
• Study Completion: May 5, 2016
• Last Updated: November 19, 2019
• Results First Posted: November 6, 2019

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)