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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00820027
Recruitment Status : Completed
First Posted : January 9, 2009
Results First Posted : April 7, 2020
Last Update Posted : April 7, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Pain, Postoperative Drug: Etoricoxib 90 mg Drug: Etoricoxib 120 mg Drug: Ibuprofen 600 mg Drug: Matching Placebo for Etoricoxib 120 mg Drug: Matching Placebo for Etoricoxib 90 mg Drug: Matching Placebo for Ibuprofen Drug: Morphine Drug: Oxycodone Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 776 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled, Multiple-Dose, Clinical Trial to Study the Safety and Efficacy of MK0663/Etoricoxib and Ibuprofen in the Treatment of Postorthopedic Knee Replacement Surgery Pain
Actual Study Start Date : December 15, 2008
Actual Primary Completion Date : December 13, 2010
Actual Study Completion Date : December 14, 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Knee Replacement
Drug Information available for: Ibuprofen

Arm Intervention/treatment
Experimental: Etoricoxib 90 mg
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
One 90 mg tablet once daily
Other Name: MK-0663

Drug: Matching Placebo for Etoricoxib 120 mg
Two tablets once daily

Drug: Matching Placebo for Ibuprofen
One tablet three times daily

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

Drug: Oxycodone
5 mg as needed

Experimental: Etoricoxib 120 mg
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
Two 60 mg tablets once daily
Other Name: MK-0663

Drug: Matching Placebo for Etoricoxib 90 mg
One tablet once daily

Drug: Matching Placebo for Ibuprofen
One tablet three times daily

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

Drug: Oxycodone
5 mg as needed

Active Comparator: Ibuprofen 1800 mg
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
One tablet three times daily

Drug: Matching Placebo for Etoricoxib 120 mg
Two tablets once daily

Drug: Matching Placebo for Etoricoxib 90 mg
One tablet once daily

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

Drug: Oxycodone
5 mg as needed

Placebo Comparator: Placebo
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
Two tablets once daily

Drug: Matching Placebo for Etoricoxib 90 mg
One tablet once daily

Drug: Matching Placebo for Ibuprofen
One tablet three times daily

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

Drug: Oxycodone
5 mg as needed




Primary Outcome Measures :
  1. Average Change From Baseline for Pain Intensity at Rest Over Days 1 to 3 (Etoricoxib vs. Placebo) [ Time Frame: Baseline and Days 1-3 ]
    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.

  2. Average Total Daily Dose of Postoperative Morphine Over Days 1 to 3 (Etoricoxib vs. Placebo) [ Time Frame: Days 1-3 ]
    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.

  3. Percentage of Participants With at Least One Adverse Event of Congestive Heart Failure, Pulmonary Edema, or Cardiac Failure [ Time Frame: Up to 21 days ]
    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.

  4. Percentage of Participants With at Least One Edema-Related AE [ Time Frame: Up to 21 days ]
    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.

  5. Percentage of Participants With at Least One Hypertension-Related AE [ Time Frame: Up to 21 days ]
    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.

  6. Percentage of Participants With at Least One Opioid-Related AE [ Time Frame: Up to 21 days ]
    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.

  7. Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 7 days ]
    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.


Secondary Outcome Measures :
  1. Average Change From Baseline for Pain Intensity at Rest Over Days 1 to 3 (Etoricoxib vs. Ibuprofen) [ Time Frame: Baseline and Days 1-3 ]
    The pain intensity difference was measured at rest over Days 1 through 3 in participants treated with etoricoxib (120 mg, 90 mg) compared to ibuprofen 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 ibuprofen 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.

  2. Average Total Daily Dose of Postoperative Morphine Over Days 1 to 3 (Etoricoxib vs. Ibuprofen) [ Time Frame: Days 1-3 ]
    The difference in average total daily dose of morphine used over Days 1 through 3 between participants treated with etoricoxib (120 mg, 90 mg) or ibuprofen 1800 mg (administered as 600 mg three times daily, every 8 hours) in the treatment of pain following total knee replacement orthopedic surgery was assessed. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00820027


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00820027    
Other Study ID Numbers: 0663-098
2009_502 ( Other Identifier: Merck Registration Number )
First Posted: January 9, 2009    Key Record Dates
Results First Posted: April 7, 2020
Last Update Posted: April 7, 2020
Last Verified: March 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Ibuprofen
Etoricoxib
Morphine
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase 2 Inhibitors