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

ABSTRACT: 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.

SUBMITTER: Singla N

PROVIDER: S-EPMC6157956 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Singla Neil N Bindewald Matthew M Singla Sonia S Leiman David D Minkowitz Harold H McCallum Stewart W SW Mack Randall J RJ Keller Rosemary R Freyer Alex A Du Wei W

Plastic and reconstructive surgery. Global open 20180619 6

<h4>Background</h4>A nanocrystal intravenous (IV) formulation of meloxicam is being studied with the aim of providing postoperative analgesia.<h4>Methods</h4>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 (SPID<sub>24</sub>).<h4>Results</h4>Meloxicam IV-treated subjects had a statistically signifi ...[more]

PMID: 30276064

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Project description:BackgroundAn 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.MethodsWomen (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.ResultsSubjects 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.ConclusionsA 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.

Project description:PurposeAlthough analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP.Patients and methodsData were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13-16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day.ResultsMean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema.ConclusionPregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity.Clinicaltrialsgov identifiersNCT0039490130, NCT0055347522, NCT0040774524.

Project description:IntroductionThis study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model.MethodsThis was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo. Primary endpoint was summary of pain intensity differences over 48 h (SPID48). Key secondary endpoints included SPID24, total consumption of rescue analgesia, and patient global assessment of efficacy (PGA). Safety assessments included treatment emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms (ECGs). Assessment of the dose-response was an important objective of the study.ResultsThe study established a dose response, with IV tramadol 50 mg demonstrating statistically significant benefit (p < 0.05) over placebo for primary and all key secondary efficacy endpoints, whereas tramadol 25 mg demonstrated intermediate results between the 50 mg and placebo arms. IV tramadol 50 mg was well tolerated; most common TEAEs were nausea and vomiting; and there were no meaningful differences among treatments for vital signs, ECG, and laboratory assessments. The largest proportion of patients completed tramadol 50 mg (98.6%) compared to tramadol 25 mg (91.8%) and placebo (88.2%).ConclusionIV tramadol 50 mg was effective and well tolerated as treatment for postoperative pain following bunionectomy surgery, while IV tramadol 25 mg, although well tolerated, was judged an ineffective dose for the treatment of pain in this setting. IV tramadol 50 mg was further developed in the registrational program for the USA.Trial registrationClinicalTrials.gov identifier, NCT03290378.

Project description:BackgroundOliceridine (TRV130), a novel ?-receptor G-protein pathway selective (?-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low ?-arrestin recruitment to the ? receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration).MethodsPatients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours.ResultsTwo hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively (P=0.0001 and P=0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P<0.0001 versus placebo). A lower prevalence of adverse events (AEs) related to nausea, vomiting, and respiratory function was observed with the oliceridine regimens than with morphine (P<0.05). Other AEs with oliceridine were generally dose-related and similar in nature to those observed with conventional opioids; no serious AEs were reported with oliceridine.ConclusionThese results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine.

Dataset Information

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

Publications

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

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