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

Pain, Postoperative Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00820027
• Other study ID #: 0663-098
• Secondary ID: 2009_502
• Status: Completed
• Phase: Phase 3
• Start date: December 15, 2008
• Est. completion date: December 14, 2010

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 776
• Est. completion date: December 14, 2010
• Est. primary completion date: December 13, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• Etoricoxib 90 mg
One 90 mg tablet once daily
• Etoricoxib 120 mg
Two 60 mg tablets once daily
• Ibuprofen 600 mg
One tablet three times daily
• Matching Placebo for Etoricoxib 120 mg
Two tablets once daily
• Matching Placebo for Etoricoxib 90 mg
One tablet once daily
• Matching Placebo for Ibuprofen
One tablet three times daily
• Morphine
As needed via patient-controlled analgesia (PCA) device or as a bolus intravenous injection
• Oxycodone
5 mg as needed

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Average Change From Baseline for Pain Intensity at Rest Over Days 1 to 3 (Etoricoxib vs. Ibuprofen)	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.	Baseline and Days 1-3
Secondary	Average Total Daily Dose of Postoperative Morphine Over Days 1 to 3 (Etoricoxib vs. Ibuprofen)	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.	Days 1-3