A Phase 3, Randomized, Placebo-Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery.
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SUBMITTER: Bergese SD
PROVIDER: S-EPMC6899482 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC5947566 | biostudies-literature
Project description: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.
| S-EPMC6157956 | biostudies-literature
Project description:ObjectiveA Phase 3 randomized multicenter, double-blind, placebo-controlled trial (NCT02720692) compared once-daily intravenous (IV) meloxicam 30 mg to placebo, when added to the standard of care pain management regimens, in adults with moderate-to-severe pain following major elective surgery and concluded that meloxicam IV had a safety profile similar to placebo and reduced opioid consumption.MethodsIn this post hoc subgroup analysis of orthopedic surgery subjects, 379 subjects received meloxicam IV 30 mg or IV-administered placebo every 24 hrs for ≤7 doses. Safety was assessed via AEs, laboratory tests, vital signs, and ECG, with an emphasis on specific AEs, including injection site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound healing events. Daily opioid consumption was assessed during treatment.ResultsAmong meloxicam IV-treated subjects, 64.7% experienced ≥1 AE versus 68.8% of placebo-treated subjects. Investigators assessed most AEs to be mild or moderate in intensity and unrelated to treatment. Total opioid consumption (36.8 mg versus 50.3 mg IV morphine equivalent dose; P=0.0081) and opioid consumption during time points 0‒24, 24‒48, 0‒48, and 0‒72 hrs were statistically significantly lower in the meloxicam IV group.ConclusionMeloxicam IV demonstrated no significant differences in the number and frequency of AEs versus placebo in subjects following orthopedic surgery. Opioid consumption was reduced in the meloxicam IV group versus placebo.Trial registrationClinicalTrials.gov (Identifier: NCT02720692).
| S-EPMC6982445 | biostudies-literature
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.
| S-EPMC7245636 | biostudies-literature
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.
| S-EPMC9788969 | biostudies-literature
Project description:Background : The incidence of moderate to severe pain is high among patients undergoing spinal surgery. Nefopam can be used as an adjuvant analgesic postoperatively after spine surgery. The study aimed to assess the analgesic efficacy and side effects of nefopam on 24-hour postoperative morphine consumption after spine surgery. Methods : The study is a randomized, double-blinded, placebo-controlled trial. A total of 96 patients were randomized into 4 treatment groups, 24 each. In group 1, patients received normal saline before surgical incision and before the end of surgery. In group 2, patients received 30 mg nefopam before surgical incision and normal saline before the end of surgery. In group 3, patients received normal saline before surgical incision and 30 mg of nefopam before the end of surgery. In group 4, patients received 30 mg of nefopam in both timings. Patient-controlled analgesia morphine was used for the postoperative period. Outcomes were to determine 24-hour morphine consumption and incidence of side effects. Results : Of 96 patients enrolled, 21 in placebo-placebo, 22 in nefopam-placebo, 22 in placebo-nefopam and 21 in nefopam-nefopam groups completed the study. Analysis of the Kruskal-Wallis test shows no significant difference in 24-hour postoperative morphine consumption between four groups, which were 18 [IQR 13.5-29], 20 [IQR 11-28.3], 17 [IQR 11.5-28.5], 13 [IQR 8.5-18.5] mg., respectively (p = 0.223). Incidence of side effects, including tachycardia, sedation, sweating and nausea/ vomiting, did not differ. Conclusions : Adding perioperative nefopam to opioid analgesic does not improve analgesic efficacy in patients who underwent spine surgery. Registration : Thai Clinical Trials Registry ID TCTR20171115001; registered on 15 November 2017.
| S-EPMC7477643 | biostudies-literature
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.
| S-EPMC6530966 | biostudies-literature
Project description:BackgroundMajor abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection.MethodsThis was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline. The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1-3 h (T1) and 24 h (T2) post-surgery.ResultsSyndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups.ConclusionsLidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated.Trial registration« ISRCTN Registry » identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.
| S-EPMC7310453 | biostudies-literature
Project description:OBJECTIVES:The primary objective of this randomized trial was to compare thoracic epidural analgesia (TEA) to intravenous patient-controlled analgesia (IV-PCA) for pain control over the first 48 hours after hepatopancreatobiliary (HPB) surgery. Secondary endpoints were patient-reported outcomes, total narcotic utilization, and complications. BACKGROUND:Although adequate postoperative pain control is critical to patient and surgeon success, the optimal analgesia regimen in HPB surgery remains controversial. METHODS:Using a 2.5:1 randomization strategy, 140 patients were randomized to TEA (N = 106) or intravenous patient-controlled analgesia (N = 34). Patient-reported pain was measured on a Likert scale (0-10) at standard time intervals. Cumulative pain area under the curve was determined using the trapezoidal method. RESULTS:Between the study groups key demographic, comorbidity, clinical, and operative variables were equivalently distributed. The median area under the curve of the postoperative time 0- to 48-hour pain scores was lower in the TEA group (78.6 vs 105.2 pain-hours, P = 0.032) with a 35% reduction in patients experiencing ?7/10 pain (43% vs 62%, P = 0.07). Patient-reported outcomes and total opiate use further supported the benefit of TEA on patient experience. Anesthesia-related events requiring change in analgesic therapy were comparable (12.2% vs 2.9%, respectively, P = 0.187). Grade 3 or higher surgical complications (6.6% vs 9.4%), median length of stay (6 days vs 6 days), readmission (1.9% vs 3.1%), and return to the operating room (0.9% vs 3.1%) were similar (all P > 0.05). There were no mortalities in either group. CONCLUSIONS:In major HPB surgery, TEA provides a superior patient experience through improved pain control and less narcotic use, without increased length of stay or complications.
| S-EPMC5784834 | biostudies-literature
Project description:BACKGROUND:Regadenoson is a selective A2A adenosine receptor agonist indicated for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. However, the safety, tolerability, and plasma concentrations associated with repeated doses have not previously been assessed. METHOD AND RESULTS:Healthy males and females were randomized to receive intravenous regadenoson [100 ?g (3 doses), 200 ?g (3 doses), or 400 ?g (2 doses)], or placebo (2 or 3 doses; 0.9% sodium chloride); all doses 10 minutes apart. The primary endpoint was vital sign measurements (blood pressure and heart rate). Secondary endpoints included 12-lead electrocardiogram measurements, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and adverse events. Thirty-six subjects were randomized and completed the study. Plasma concentrations of regadenoson increased in a dose-related manner and with successive doses. No consistent effect was observed for systolic blood pressure, although diastolic blood pressure was slightly lower than placebo for all regadenoson groups. Transient, dose-dependent increases in heart rate were observed in all regadenoson groups. There were no serious adverse events; 27 adverse events occurred in 14 regadenoson-treated subjects vs two events in two placebo-treated subjects. CONCLUSION:Repeated doses of regadenoson appeared to be safe and well tolerated in healthy subjects.
| S-EPMC5250646 | biostudies-literature