Economic Impact of Preoperative Meloxicam IV Administration in Total Knee Arthroplasty: A Randomized Trial Sub-Study.

We evaluated the economic impact associated with preoperative meloxicam IV 30 mg vs placebo administration among adult total knee arthroplasty (TKA) recipients enrolled in Phase IIIB NCT03434275 trial. Data on total hospital costs and length of stay (LOS) obtained from the trial were compared between meloxicam IV 30 mg and placebo groups. Patients in the meloxicam IV 30 mg vs placebo group (n = 93 vs 88) incurred an adjusted $2,266 (95% CI: -$1,035, $5,116; p = 0.1689) lower total hospital costs and an adjusted 8.6% (95% confidence interval [CI]: -2.0%, 18.1%; p = 0.1082) shorter LOS. While statistically non-significant, based on 95% CIs, the results from this sub-study may suggest a favorable impact associated with meloxicam IV 30 mg on hospital costs and LOS.

Safety and Efficacy of Perioperative Intravenous Meloxicam for Moderate-to-Severe Pain Management in Total Knee Arthroplasty: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of perioperative meloxicam IV 30 mg on opioid consumption in primary total knee arthroplasty (TKA). DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial. SUBJECTS: In total, 181 adults undergoing elective primary TKA. METHODS: Subjects received meloxicam 30 mg or placebo via an IV bolus every 24 hours, the first dose administered prior to surgery as part of a multimodal pain management protocol. The primary efficacy parameter was total opioid use from end of surgery through 24 hours. RESULTS: Meloxicam IV was associated with less opioid use versus placebo during the 24 hours after surgery (18.9 ± 1.32 vs 27.7 ± 1.37 mg IV morphine equivalent dose; P < 0.001) and was superior to placebo on secondary endpoints, including summed pain intensity (first dose to 24 hours postdosing, first dose to first assisted ambulation, and first dose to discharge) and opioid use (48-72 hrs., 0-48 hrs., 0-72 hrs., hour 0 to end of treatment, and the first 24 hours after discharge). Adverse events (AEs) were reported for 69.9% and 92.0% of the meloxicam IV and placebo groups, respectively; the most common AEs were nausea (40% vs. 59%), vomiting (16% vs 22%), hypotension (14% vs 15%), pruritus (15% vs 11%), and constipation (11% vs 13%). CONCLUSIONS: Perioperative meloxicam IV 30 mg as part of a multimodal analgesic regimen for elective primary TKA reduced opioid consumption in the 24-hour period after surgery versus placebo and was associated with a lower incidence of AEs typically associated with opioid use.

Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate post-operative period: a Phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis.

Aim: Evaluate safety/efficacy of intravenous meloxicam in a colorectal enhanced recovery after surgery protocol. Methods: Adults undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis received meloxicam IV 30 mg (n = 27) or placebo (n = 28) once daily beginning 30 min before surgery. Results: Adverse events: meloxicam IV, 85%; placebo, 93%. Adverse events commonly associated with opioids: 41 versus 61% - including nausea (33 vs 50%), vomiting (19 vs 18%) and ileus (4 vs 18%). Wound healing satisfaction scores (physician-rated), clinical laboratory findings and vital signs were similar in both groups. No anastomotic leaks were reported. Opioid consumption, postoperative pain intensity, length of stay and times to first bowel sound, first flatus and first bowel movement were significantly lower with meloxicam IV versus placebo. Most subjects (>92%) were satisfied with postoperative pain medication. Conclusion: Meloxicam IV was generally well tolerated and associated with decreased opioid consumption, lower resource utilization and functional benefits. Clinical Trial Registration: NCT03323385 (ClinicalTrials.gov).

Platelet Function: Meloxicam Intravenous in Whole Blood Samples From Healthy Volunteers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.

Analgesic Efficacy and Safety of Intravenous Meloxicam in Subjects With Moderate-to-Severe Pain After Open Abdominal Hysterectomy: A Phase 2 Randomized Clinical Trial.

BACKGROUND: An intravenous (IV) formulation of meloxicam was developed for moderate-to-severe pain management. This study evaluated the safety and efficacy of meloxicam IV after open abdominal hysterectomy. Meloxicam IV is an investigational product not yet approved by the US Food and Drug Administration. METHODS: Women (N = 486) with moderate-to-severe pain after open abdominal hysterectomy were enrolled in this multicenter, randomized, double-blind, placebo- and active-controlled trial. Subjects were randomized to receive a single dose of meloxicam IV (5-60 mg), placebo, or morphine (0.15 mg/kg) in ≤6 hours after morphine dosing on postoperative day 1 and were evaluated for 24 hours. Rescue morphine (≈0.15 mg/kg IV) was available if needed for pain not relieved by the study medication. In an open-label extension (N = 295), meloxicam IV was administered once daily for the remaining hospital stay (or per the investigator's discretion). The coprimary efficacy end points were the summed pain intensity difference (SPID24) and total pain relief (TOTPAR24) from hour 0 to 24 hours after dosing. Effect size, the standardized difference between means reported in standard deviation (SD) units, was calculated to indicate the magnitude of the difference in the mean analgesic effect measured for different intervention groups. RESULTS: Subjects who received morphine or meloxicam IV had a median time to first perceptible pain relief within 6-8 minutes. Morphine and meloxicam IV 5-60 mg produced statistically significant differences than placebo in SPID24 and TOTPAR24. SPID24 (standard error [SE]) for meloxicam IV 5-60 mg ranged from -56276.8 (3926.46) to -33517.1 (3930.1; P < .001); SPID24 (SE) for morphine and placebo were -29615.8 (3869.2; P < .001) and 4555.9 (3807.1), respectively. SPID24 effect sizes (95% confidence intervals) for the 60, 30, 15, 7.5, and 5 mg meloxicam IV doses and morphine were 1.93 (1.61-2.25), 2.00 (1.65-2.35), 1.70 (1.35-2.05), 1.28 (0.95-1.60), 1.25 (0.90-1.61), and 1.12 (0.77-1.45) SDs, respectively. TOTPAR24 (SE) for meloxicam IV 5-60 mg ranged from 3104.5 (155.28) to 4130.4 (191.17; P < .001); TOTPAR24 (SE) for morphine and placebo were 2723.3 (188.4; P < .001) and 1100.6 (185.4), respectively. TOTPAR24 effect sizes (95% confidence interval) for the 60, 30, 15, 7.5, and 5 mg meloxicam IV doses and morphine were 2.03 (1.70-2.35), 2.05 (1.70-2.40), 1.78 (1.43-2.13), 1.35 (1.03-1.67), 1.37 (1.01-1.72), and 1.10 (0.75-1.45) SDs, respectively. The mean total opioid consumed (SD) during the double-blind phase was 4.6 (8.17), 5.3 (8.85), 5.9 (7.85), 8.5 (9.67), 9.3 (9.47), 9.6 (8.12), and 16.0 (10.15) mg for patients in the 60, 30, 15, 7.5, and 5 mg meloxicam IV, morphine, and placebo groups, respectively. Generally, meloxicam IV was well tolerated, evidenced by the incidence of adverse events compared to placebo and lack of deaths and treatment-related serious adverse events. CONCLUSIONS: A meloxicam IV dose of 5-60 mg was generally well tolerated and appeared to reduce opioid consumption in subjects with moderate-to-severe pain after open abdominal hysterectomy. Once-daily administration of meloxicam IV produced analgesic effect within 6-8 minutes postdose that was maintained over a 24-hour dosing interval.

Efficacy and Safety of Intravenous Meloxicam in Subjects with Moderate-to-severe Pain Following Abdominoplasty.

BACKGROUND: A nanocrystal intravenous (IV) formulation of meloxicam is being studied with the aim of providing postoperative analgesia. METHODS: This randomized, multicenter, double-blind, placebo-controlled trial evaluated meloxicam IV 30 mg or placebo (≤ 3 doses) in 219 subjects undergoing abdominoplasty. The primary endpoint was the summed pain intensity difference over 24 hours postdose (SPID24). RESULTS: Meloxicam IV-treated subjects had a statistically significant reduction in the least squares mean of SPID24 compared with placebo-treated subjects (-4,262.1 versus -3,535.7; P = 0.0145). Meloxicam IV was associated with statistically significant differences over placebo on several other secondary endpoints, including other SPID intervals (ie, SPID12, SPID48, and SPID24-48), achievement of perceptible pain relief, the proportion of subjects with a ≥ 30% improvement in the first 24 hours, and Patient Global Assessment of pain at hour 48. Meloxicam IV was also associated with a reduction in the number of subjects receiving opioid rescue medication during hours 24-48 and the total number of doses of opioid rescue analgesia. Meloxicam IV was generally well tolerated, with the numbers and frequencies of adverse events similar to that of the placebo group. There was no evidence of an increased risk of adverse events commonly associated with nonsteroidal anti-inflammatory drugs including bleeding, thrombotic, cardiovascular, renal, hepatic, cardiovascular, injection site, and wound healing events. CONCLUSION: Meloxicam IV provided sustained pain relief and generally was well tolerated in subjects with moderate-to-severe pain following abdominoplasty.

Efficacy and Safety of Intravenous Meloxicam in Patients With Moderate-to-Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-controlled Trial.

OBJECTIVE: To evaluate the analgesic efficacy and safety of a novel intravenous (IV) formulation of meloxicam (30 mg) in patients with moderate-to-severe pain following a standardized, unilateral bunionectomy with first metatarsal osteotomy and internal fixation. MATERIALS AND METHODS: Patients who met the criteria for moderate-to-severe postoperative pain were randomized to receive bolus injections of meloxicam IV 30 mg (n=100) or placebo (n=101) administered once daily. The primary efficacy endpoint was the Summed Pain Intensity Difference over 48 hours (SPID48). Secondary efficacy endpoints included sum of time-weighted pain intensity differences (SPID) values at other timepoints/intervals, time to first use of rescue analgesia, and number of rescue doses taken. Safety assessments included the incidence of adverse events (AEs), physical examinations, laboratory tests, 12-lead electrocardiography, and wound healing. RESULTS: Patients randomized to meloxicam IV 30 mg exhibited a statistically significant difference in SPID48 versus the placebo group (P=0.0034). Statistically significant differences favoring meloxicam IV over placebo were also observed for secondary efficacy endpoints, including SPID at other times/intervals (SPID6: P=0.0153; SPID12: P=0.0053; SPID24: P=0.0084; and SPID24-48: P=0.0050) and first use of rescue medication (P=0.0076). Safety findings indicated that meloxicam IV 30 mg was generally well tolerated; no serious AEs or bleeding events were observed. Most AEs were assessed by the investigator to be mild in intensity, and no patients discontinued due to AEs. There were no meaningful differences between the study groups in vital signs, electrocardiographic findings, or laboratory assessments. In most cases, investigators found that wound healing followed a normal course and mean wound-healing satisfaction scores were similar for meloxicam IV 30 mg and placebo. DISCUSSION: Meloxicam IV doses of 30 mg provided effective pain relief when administered once daily by bolus injection to patients with moderate-to-severe pain following bunionectomy, and had an acceptable safety profile.

Evaluation of the safety and efficacy of an intravenous nanocrystal formulation of meloxicam in the management of moderate-to-severe pain after bunionectomy.

OBJECTIVE: This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of an intravenous (IV) nanocrystal formulation of meloxicam in subjects with moderate-to-severe pain following a standardized unilateral bunionectomy. METHODS: Fifty-nine subjects aged 18-72 years were randomized to receive doses of either 30 mg (n=20) or 60 mg (n=20) meloxicam IV or placebo (n=19), administered once daily as bolus IV injections over 15-30 seconds (two or three doses). Safety, the primary objective, was assessed by physical examination, clinical laboratory tests, and the incidence of adverse events (AEs). Efficacy was evaluated by examining summed pain intensity differences over the first 48 hours (SPID48) using analysis of covariance models. Use of opioid rescue analgesic agents was evaluated. RESULTS: Generally, AEs were mild-to-moderate in intensity, and their incidence was similar across the three treatment groups. No serious AEs were reported; there were no withdrawals due to AEs, including injection-related AEs. The estimated effect size for SPID48 versus placebo was 1.15 and 1.01 for meloxicam IV doses 30 mg and 60 mg, respectively (P≤0.01). Both doses produced significantly greater pain reductions versus placebo (P≤0.05) at all evaluated times/ intervals during the 48-hour period. The proportions of subjects with ≥30% and ≥50% overall reduction in pain from baseline after 6 and 24 hours were significantly higher with meloxicam IV 30 mg doses versus placebo, but not with meloxicam IV 60 mg doses. The time to first use of rescue medication was significantly longer versus placebo with meloxicam IV 60 mg (P<0.05), but not with meloxicam IV 30 mg doses. CONCLUSION: Meloxicam IV was generally safe and well tolerated in subjects with moderate-to-severe post-bunionectomy pain. Once-daily administration of meloxicam IV 30 mg and 60 mg exhibited rapid onset of analgesia (as early as 15 minutes) with maintenance of analgesic effect for two consecutive 24-hour periods.

A Randomized Double-Blind Controlled Trial of Intravenous Meloxicam in the Treatment of Pain Following Dental Impaction Surgery.

This randomized, controlled phase 2 study was conducted to evaluate the analgesic efficacy, safety, and tolerability of single intravenous (IV) doses of 15 mg, 30 mg, and 60 mg meloxicam compared with oral ibuprofen 400 mg and placebo after dental impaction surgery. The primary efficacy end point was the sum of time-weighted pain intensity differences for 0-24 hours postdose. Among 230 evaluable subjects, meloxicam IV 60 mg produced the greatest reduction in pain, followed by the 30-mg and 15-mg doses. Statistically significant differences in summed pain intensity differences over 24 hours were demonstrated for each active-treatment group vs placebo (favoring active treatment) and for meloxicam IV 30 mg and 60 mg vs ibuprofen 400 mg (favoring meloxicam IV). Moreover, there was a statistically significant dose response for meloxicam IV 15 mg to 60 mg. The onset of action for meloxicam IV was rapid and sustained; significant differences in pain intensity differences were detected as early as 10 minutes postdose and lasted through the 24-hour postdose period. Subjects in the meloxicam IV groups were more likely than placebo recipients to achieve perceptible and meaningful pain relief and were less likely to use rescue medication. Patient-reported global evaluation showed that meloxicam IV 60 mg had the highest rating. There were no deaths, serious adverse events, or discontinuations due to adverse events. The incidence of subjects with ≥1 treatment-emergent adverse event was greatest in the placebo group, followed by the groups that received ibuprofen, meloxicam IV 15 mg, 30 mg, and 60 mg. Nausea was the most commonly reported treatment-emergent adverse event. CLINICAL TRIAL REGISTRATION NUMBER: NCT00945763.