Study of MK-0663/Etoricoxib in Postorthopedic Knee Replacement Surgery Pain (MK-0663-098)

NCT00820027 | Completed Phase 3 Results

• 2 other identifiers: 0663-0982009_502
• Study Type: interventional
• Target: 776
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of Etoricoxib compared to placebo and ibuprofen in the treatment of postoperative pain associated with unilateral total knee replacement surgery. The hypotheses for this study were that the average pain intensity difference (at rest) in participants treated with Etoricoxib (120 mg, 90 mg) is superior to placebo, the average total daily dose of morphine in participants treated with Etoricoxib (120 mg, 90 mg) is less than in participants treated with placebo, and that Etoricoxib (120 mg, 90 mg) will be generally safe and well tolerated by participants treated for pain following total knee replacement orthopedic surgery.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (7)

• Average Change From Baseline for Pain Intensity at Rest Over Days 1 to 3 (Etoricoxib vs. Placebo)

  The pain intensity difference was measured at rest over Days 1 through 3 in patients treated with etoricoxib (120 mg, 90 mg) compared to placebo for the treatment of pain following total knee replacement orthopedic surgery. Pain intensity difference at rest was measured on a numerical rating scale (NRS) from 0 - 10 points (0=no pain, to 10=pain as bad as you can imagine). Comparison to placebo was conducted in a step-down manner (the 90-mg dose was evaluated only if the null hypotheses for co-primary endpoints \[Pain Intensity Difference (PID) and Morphine\] 120-mg doses were rejected). The primary analyses for change from baseline in average pain intensity at rest over Days 1 to 3 was performed using the longitudinal data analysis (LDA) method with the terms for baseline pain intensity (moderate or severe), type of anesthesia (spinal or general), treatment, day, and the interaction of day by treatment.

  Baseline and Days 1-3

• Average Total Daily Dose of Postoperative Morphine Over Days 1 to 3 (Etoricoxib vs. Placebo)

  The average total dose of morphine was assessed when participant received etoricoxib 120 milligram(mg)/90 mg compared to placebo. Opioids taken were converted to mg morphine equivalents according to the following conventions: 1 mg morphine sulphate=1 mg morphine,1 mg morphine hydrochloride=1.17 mg morphine. A 5 mg oxycodone tablet=2.5 mg morphine,12.5 mg meperidine =1.67 mg morphine. Least-squares mean back-transformed; estimate obtained from longitudinal analysis of variance (ANOVA) model on log-transformed morphine dose with terms for baseline pain intensity(moderate or severe),type of anesthesia (spinal, general), treatment, day, and the interaction of day by treatment.

  Days 1-3

• Percentage of Participants With at Least One Adverse Event of Congestive Heart Failure, Pulmonary Edema, or Cardiac Failure

  An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

  Up to 21 days

• Percentage of Participants With at Least One Edema-Related AE

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE. Edema is swelling caused by excess fluid trapped in body tissues.

  Up to 21 days

• Percentage of Participants With at Least One Hypertension-Related AE

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

  Up to 21 days

• Percentage of Participants With at Least One Opioid-Related AE

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE. Opioid-related AEs include nausea, vomiting, constipation, somnolence, respiratory depression, urinary retention and ileus.

  Up to 21 days

• Percentage of Participants Who Discontinued Study Drug Due to an AE

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study product, is also an AE.

  Up to 7 days

Secondary Outcomes (2)

• Average Change From Baseline for Pain Intensity at Rest Over Days 1 to 3 (Etoricoxib vs. Ibuprofen)

  Baseline and Days 1-3

• Average Total Daily Dose of Postoperative Morphine Over Days 1 to 3 (Etoricoxib vs. Ibuprofen)

  Days 1-3

Study Arms (4)

Etoricoxib 90 mg

EXPERIMENTAL

Participants received etoricoxib 90 mg once daily, matching placebo to etoricoxib 120 mg once daily, and matching placebo to ibuprofen 600 mg every 8 hours for 7 days.

Drug: Etoricoxib 90 mg; Drug: Matching Placebo for Etoricoxib 120 mg; Drug: Matching Placebo for Ibuprofen; Drug: Morphine; Drug: Oxycodone

Etoricoxib 120 mg

EXPERIMENTAL

Participants received etoricoxib 120 mg once daily, matching placebo to etoricoxib 90 mg once daily, and matching placebo to ibuprofen 600 mg every 8 hours for 7 days.

Drug: Etoricoxib 120 mg; Drug: Matching Placebo for Etoricoxib 90 mg; Drug: Matching Placebo for Ibuprofen; Drug: Morphine; Drug: Oxycodone

Ibuprofen 1800 mg

ACTIVE COMPARATOR

Participants received ibuprofen 600 mg every 8 hours, matching placebo to etoricoxib 120 mg once daily, and matching placebo to etoricoxib 90 mg once daily for 7 days.

Drug: Ibuprofen 600 mg; Drug: Matching Placebo for Etoricoxib 120 mg; Drug: Matching Placebo for Etoricoxib 90 mg; Drug: Morphine; Drug: Oxycodone

Placebo

PLACEBO COMPARATOR

Participants received matching placebo to etoricoxib 90 mg and matching placebo to etoricoxib 120 mg once daily, and matching placebo to ibuprofen every 8 hours for 7 days.

Drug: Matching Placebo for Etoricoxib 120 mg; Drug: Matching Placebo for Etoricoxib 90 mg; Drug: Matching Placebo for Ibuprofen; Drug: Morphine; Drug: Oxycodone

Interventions

Etoricoxib 90 mg DRUG

One 90 mg tablet once daily

Also known as: MK-0663

Etoricoxib 90 mg

Etoricoxib 120 mg DRUG

Two 60 mg tablets once daily

Also known as: MK-0663

Etoricoxib 120 mg

Ibuprofen 600 mg DRUG

One tablet three times daily

Ibuprofen 1800 mg

Matching Placebo for Etoricoxib 120 mg DRUG

Two tablets once daily

Etoricoxib 90 mg; Ibuprofen 1800 mg; Placebo

Matching Placebo for Etoricoxib 90 mg DRUG

One tablet once daily

Etoricoxib 120 mg; Ibuprofen 1800 mg; Placebo

Matching Placebo for Ibuprofen DRUG

One tablet three times daily

Etoricoxib 120 mg; Etoricoxib 90 mg; Placebo

Morphine DRUG

As needed via patient-controlled analgesia (PCA) device or as a bolus intravenous injection

Etoricoxib 120 mg; Etoricoxib 90 mg; Ibuprofen 1800 mg; Placebo

Oxycodone DRUG

5 mg as needed

Etoricoxib 120 mg; Etoricoxib 90 mg; Ibuprofen 1800 mg; Placebo

Eligibility Criteria

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

You may qualify if:

• \- Is in generally good health and is scheduled to have a total knee replacement

You may not qualify if:

• Is allergic, intolerant to, or has a history of a significant clinical or laboratory adverse experience associated with etoricoxib or other cyclooxygenase-2 (COX-2) inhibitors/non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, morphine, or oxycodone, or has hypersensitivity to aspirin, or other NSAIDs
• Has uncontrolled hypertension
• Is currently a user of any illicit drugs, or has a history of drug or alcohol abuse within the past 5 years

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Rawal N, Viscusi E, Peloso PM, Minkowitz HS, Chen L, Shah S, Mehta A, Chitkara DK, Curtis SP, Papanicolaou DA. Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial. BMC Musculoskelet Disord. 2013 Oct 24;14:300. doi: 10.1186/1471-2474-14-300.

  PMID: 24156640 DERIVED

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Etoricoxib; Ibuprofen; Morphine; Oxycodone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Codeine

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2009
• First Posted: January 9, 2009
• Study Start: December 15, 2008
• Primary Completion: December 13, 2010
• Study Completion: December 14, 2010
• Last Updated: February 9, 2022
• Results First Posted: April 7, 2020

Record last verified: 2022-02