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A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

ABSTRACT: An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consumption. The incidence of adverse events was similar between meloxicam IV- and placebo-treated subjects (63.0% versus 65.0%). Investigators assessed most adverse events as mild or moderate in intensity and unrelated to treatment. Adverse events of interest (injection-site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound-healing events) were similar between groups. Over the treatment period, meloxicam IV was associated with a 23.6% (P = .0531) reduction in total opioid use (9.2 mg morphine equivalent) compared to placebo-treated subjects. The results suggest that meloxicam IV had a safety profile similar to that of placebo with respect to numbers and frequencies of adverse events and reduced opioid consumption in subjects with moderate to severe postoperative pain following major elective surgery.

SUBMITTER: Bergese SD

PROVIDER: S-EPMC6899482 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

Bergese Sergio D SD Melson Timothy I TI Candiotti Keith A KA Ayad Sabry S SS Mack Randall J RJ McCallum Stewart W SW Du Wei W Gomez Alexis A Marcet Jorge E JE

Clinical pharmacology in drug development 20190220 8

An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consump ...[more]

PMID: 30786162

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Project description:BackgroundCoronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19.MethodsThe protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed.DiscussionThis is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.Trial registrationClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

Project description:Residual neuromuscular blockade (NMB) is an important and modifiable factor associated with prolonged mechanical ventilation after cardiac surgery. Studies evaluating the use of sugammadex for residual NMB reversal in the post-cardiac surgery ICU setting are lacking. We conducted a randomized trial to determine the efficacy of sugammadex in reducing time to extubation in patients admitted to the ICU after cardiac surgery.DesignSingle-center, randomized, double-blind, placebo-controlled trial.SettingUniversity-based cardiothoracic ICU.SubjectsPatients (n = 90) undergoing elective aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG) surgery.InterventionsParticipants were randomized to receive either sugammadex (2 mg/kg) or placebo after arrival to the ICU.Measurements and main resultsThe primary study endpoint was time from study drug administration to extubation. Of the 90 patients included in the study (45 in each group), a total of 68 patients underwent CABG, 13 AVR, and nine combined AVR and CABG. Baseline characteristics and intraoperative anesthetic medications were comparable between groups. Patients in sugammadex group had reduced time to extubation compared with the placebo group (median [interquartile range (IQR)]-sugammadex group: 126.0 min [84.0-274.0 min] vs placebo: 219.0 min [121.0-323.0 min]; difference in means [95% CI], 72.8 [1.5-144.1 min]; p = 0.01. There were no differences in negative inspiratory force (mean [sd]-sugammadex group: 33.79 cm H2O [8.39 cm H2O] vs placebo: -31.11 cm H2O [7.17 cm H2O]) and vital capacity (median [IQR]-sugammadex group: 1.1 L [0.9-1.3 L] vs placebo: 1.0 L [0.9-1.2 L]). There were no differences between groups in postoperative blood product requirement, dysrhythmias, length of ICU, or hospital stay. There were no serious adverse events in either group.ConclusionsThis randomized trial showed that the administration of sugammadex after cardiac surgery decreased time to extubation by approximately 1 hour. Larger trials may be required to confirm these findings and determine the clinical implications.

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.

Dataset Information

A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

Publications

A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.

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