Evaluation of multiday analgesia with etoricoxib in a double-blind, randomized controlled trial using the postoperative third-molar extraction dental pain model.

OBJECTIVE: To evaluate the analgesic effects of etoricoxib and comparator agents on the second and third days after oral surgery. METHODS: There were 588 patients initially randomized to placebo (n=46), etoricoxib 120 mg once daily (n=97), etoricoxib 90 mg once daily (n=191), ibuprofen 600 mg every 6 hours (n=192), and acetaminophen 600 mg/codeine 60 mg (A/C) every 6 hours (n=62) after third-molar extraction (≥2, ≥1 impacted) in a double-blind controlled trial. Patients were allowed flexible dosing on days 2 and 3; 46, 96, 190, 192, and 56 patients on placebo, etoricoxib 120 mg, etoricoxib 90 mg, ibuprofen, and A/C, respectively, continued to Day 2 of the study. Outcomes included Average and Worst Recall Pain Assessments (0 to 10 scale) and Global Assessments of Study Medication (0 to 4 scale). Rescue medication (acetaminophen 325 mg up to 4 times daily) usage was evaluated. Adverse experiences were collected and evaluated. RESULTS: Average Pain Recall scores were lower than placebo for all active treatments on Day 2 but only for etoricoxib 120 and 90 mg on Day 3. Worst Pain Recall scores were lower than placebo for only etoricoxib 120 and 90 mg on Day 2; all treatment groups were similar on day 3. Rescue medicine was used on day 2 in 57% of placebo patients, whereas use in active treatments ranged from 18% to 23%; for Day 3, rescue was used in 22% of placebo patients, whereas use in active treatments ranged from 14% to 20%. Differences in mean Patient's Global Assessment of Study Medication scores were significant for etoricoxib versus placebo (P<0.001) and for etoricoxib versus A/C (P<0.010). Nausea and vomiting were among the most common adverse events with higher frequency in the A/C group. CONCLUSIONS: Pain control was most favorable for the etoricoxib doses and ibuprofen. Global Assessments of Study Medication continued to differentiate the treatments and demonstrated greater efficacy for etoricoxib on Days 2 and 3 compared with placebo and A/C (NCT00694369).

Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.

OBJECTIVE: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively. RESEARCH DESIGN AND METHODS: In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144). Average Pain Intensity at Rest over days 1-3 (0- to 10-point numerical rating scale [NRS]) was the primary efficacy endpoint. Secondary endpoints included Average Pain Intensity upon Sitting, Standing, and Walking over days 1-3 (0- to 10-point NRS) as well as Average Total Daily Dose of Morphine over days 1-3. CLINICAL TRIAL REGISTRATION: This trial is registered on www.clinicaltrials.gov (NCT00788710). RESULTS: The least squares (LS) means (95% CI) for the primary endpoint were 3.26 (2.96, 3.55); 2.46 (2.16, 2.76); and 2.40 (2.11, 2.69) for placebo, etoricoxib 90 mg, and etoricoxib 120 mg, respectively, significantly different for both etoricoxib doses versus placebo (p < 0.001). Patients on etoricoxib 90 mg and 120 mg required ~30% less morphine per day than those on placebo (p < 0.001), which led to more rapid bowel recovery in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain ≤3/10. LIMITATIONS: A key limitation for this study was that movement-evoked pain measurements were not designated as primary endpoints. CONCLUSION: In patients undergoing total abdominal hysterectomy, etoricoxib 90 mg and 120 mg dosed preoperatively and then continued postoperatively significantly reduces both resting and movement-related pain, as well as reduced opioid (morphine) consumption that led to more rapid bowel recovery.

The VIOXX in Prostate Cancer Prevention study: cardiovascular events observed in the rofecoxib 25 mg and placebo treatment groups.

BACKGROUND: A double-blind, randomized, placebo-controlled study was designed to determine the cumulative incidence of developing prostate cancer over 6 years of treatment with rofecoxib 25 mg/day versus placebo. Before completion, this trial was terminated following the voluntary withdrawal of rofecoxib. (On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.) Here we report the cardiovascular (CV) safety data collected from this study. METHODS: A total of 4741 men (44-81 years old) exhibiting prostate-specific antigen levels (PSA) between 2.5 and 10 ng/mL were enrolled. Patients were stratified by PSA level and use of low-dose aspirin (LDA), then randomized to rofecoxib 25 mg (n = 2369) or placebo (n = 2372). Safety data were analyzed in all patients receiving > or = 1 dose of study medication. All reported thrombotic CV events occurring on-treatment or within 14 days after study drug discontinuation were adjudicated by an independent panel of clinical experts blinded to treatment assignment. Rates per 100 patient-years and relative risk (RR) of thrombotic CV events, rofecoxib vs. placebo, were determined. RESULTS: Approximately 36% of patients had > or = 2 CV risk factors or LDA indicated. Median treatment duration was 4.14 (range: 0.03-15.90) months. Twenty-nine patients (14 rofecoxib, rate 1.27; 15 placebo, rate 1.36) experienced confirmed thrombotic CV events; RR 0.94 (95% CI: 0.45, 1.94) vs. placebo. Four patients (one rofecoxib; three placebo) died due to a confirmed thrombotic event. Significantly (p = 0.002) more patients receiving rofecoxib (n = 20; 0.8%) experienced hypertension-related adverse events versus placebo (n = 2; 0.1%). There were no cases of congestive heart failure. CONCLUSIONS: Rofecoxib 25 mg and placebo demonstrated similar risk of thrombotic CV events in this limited dataset.

Evaluation of the effect of perioperative rofecoxib treatment on pain control and clinical outcomes in patients recovering from gynecologic abdominal surgery: a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND AND OBJECTIVES: In this randomized, placebo-controlled, double-blind study, the efficacy and safety of rofecoxib 50 mg was evaluated in patients undergoing major abdominal gynecologic surgery. METHODS: Patients were randomized to receive rofecoxib 50 mg (n = 81) or placebo (n = 83) approximately 2 hours before total abdominal hysterectomy or myomectomy and once daily over the ensuing 4 days. Clinical measurements included average daily opioid use over the 5-day period (primary endpoint), pain intensity on movement, and opioid-related side effects. RESULTS: Patients receiving rofecoxib required 32% less (P = .001) intravenous and oral opioids to relieve their postoperative pain from days 1 to 5 (primary endpoint), used 21% less (P = .011) on day 1, and 42% less (P < .001) from days 2 to 5. The rofecoxib group experienced less pain upon movement (P < .001), less sedation (P = .007), and a 24% reduction in the rate of antiemetic intake (P = .037) over the first 72 hours postsurgery. Earlier mean times to first flatus (-10.1 hours, P = .001), first bowel movement (-14.1 hours, P = .037), and time to hospital discharge (-10.9 hours; 95% confidence interval, -17.1 to -4.7) occurred in the rofecoxib group. There were no significant intergroup differences in blood loss, wound healing, or overall adverse experiences. CONCLUSIONS: Compared with placebo, perioperative administration of rofecoxib 50 mg provided significant opioid sparing, significantly better pain control, improved clinical outcomes, and was well tolerated.

Pooled analysis of thrombotic cardiovascular events in clinical trials of the COX-2 selective Inhibitor etoricoxib.

BACKGROUND: A pooled analysis of randomized clinical trials data was performed to compare the rate of thrombotic cardiovascular events (thrombotic events) in patients taking the COX-2 selective inhibitor (coxib) etoricoxib, a traditional NSAID, or placebo. METHODS: Data collected during all phase IIb/III etoricoxib clinical trials > or = 4 weeks in duration were evaluated. The pooled data set includes clinical information from approximately 6500 patient-years (PYs) of drug exposure in patients diagnosed with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), or chronic low back pain (CLBP). Patients were treated with either etoricoxib (> or = 60 mg/day), the traditional NSAIDs naproxen (1000 mg/day), ibuprofen (2400 mg/day), diclofenac (150 mg/day), or placebo. The Relative risks (RRs) based on time to first occurrence of a thrombotic event in the etoricoxib group versus the comparator traditional NSAIDs or versus placebo were determined using patient-level data. RESULTS: In the pooled dataset, a total of 74 thrombotic events occurred in 69 patients. The RRs for thrombotic events were 1.11 (95%CI: 0.32, 3.81) for etoricoxib (N = 2818) versus placebo (N = 1767); 0.83 (95%CI: 0.26, 2.64) for etoricoxib (N = 1266) versus the combined non-naproxen traditional NSAID group (ibuprofen and diclofenac; N = 718); and 1.70 (95%CI: 0.91, 3.18) for etoricoxib (N = 1960) versus naproxen (N = 1497). CONCLUSIONS: There was no discernible difference in the incidence of thrombotic events in patients treated with etoricoxib versus non-naproxen traditional NSAIDs in this limited dataset. A trend toward more events with etoricoxib versus naproxen was observed. Despite the limited dataset available for this pooled analysis, these results are consistent with findings for other coxibs.

Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489].

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA) patients. METHODS: A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks), patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks); the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study. RESULTS: Compared with placebo, the etoricoxib groups displayed significant (p < 0.05), dose-dependent efficacy for all primary endpoints in Part I; efficacy was maintained throughout the 52 weeks of the study. During the 46-week active-comparator controlled period, the etoricoxib groups demonstrated clinical efficacy that was similar to that of diclofenac 150 mg and was generally well tolerated, with a lower incidence of gastrointestinal (GI) nuisance symptoms compared with diclofenac (13.1, 14.7, and 13.5% for etoricoxib 30, 60, and 90 mg, respectively compared with 22.5% for diclofenac). CONCLUSION: In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated.