scholarly journals Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain

2019 ◽  
Vol 45 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Thomas Ottoboni ◽  
Barry Quart ◽  
Jayne Pawasauskas ◽  
Joseph F Dasta ◽  
Richard A Pollak ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Phase Ii ◽  
Analgesic Activity ◽  
Mechanism Of Action ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Extended Release ◽  
Low Dose ◽  
Clinical Results ◽  
Tissue Ph

Background and objectives Obtaining consistent efficacy beyond 12–24 hours with local anesthetics, including extended-release formulations, has been a challenging goal. Inflammation resulting from surgery lowers the pH of affected tissues, reducing neuronal penetration of local anesthetics. HTX-011, an investigational, nonopioid, extended-release dual-acting local anesthetic combining bupivacaine and low-dose meloxicam, was developed to reduce postsurgical pain through 72 hours using novel extended-release polymer technology. Preclinical studies and a phase II clinical trial were conducted to confirm the mechanism of action of HTX-011. Methods In a validated postoperative pain pig model and a phase II bunionectomy trial, the analgesic effects of HTX-011, oral meloxicam (preclinical only), liposomal bupivacaine (preclinical only) and saline placebo were evaluated. The optimal meloxicam:bupivacaine ratio for HTX-011 and the effect of HTX-011 on incisional tissue pH were also evaluated preclinically. Results Preclinical data demonstrate the ability of HTX-011 to address local tissue inflammation as demonstrated by a less acidic tissue pH, which was associated with potentiated and prolonged analgesic activity. In the phase II bunionectomy study, HTX-011 achieved superior and sustained pain relief through 72 hours after surgery compared with each component in the polymer. Conclusions Preclinical animal and clinical results confirm that the low-dose meloxicam in HTX-011 normalizes the local pH in the incision, resulting in superior and synergistic analgesic activity compared with extended-release bupivacaine. HTX-011 represents an extended-release local anesthetic with a dual-acting mechanism of action that may provide an important advancement in the treatment of postoperative pain. Trial registration number NCT02762929.

scholarly journals The Effect of Subcutaneous and Intraperitoneal Instillation of Local Anesthetics on Postoperative Pain after Laparoscopic Varicocelectomy: A Randomized Controlled Trial

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1051
Author(s):  
Zenon Pogorelić ◽  
Tea Gaberc ◽  
Miro Jukić ◽  
Goran Tintor ◽  
Ana Nevešćanin Biliškov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Postoperative Pain ◽  
Pain Intensity ◽  
Randomized Clinical Trial ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Control Group ◽  
Number Of Patients ◽  
Intraperitoneal Instillation ◽  
Time Point

Background: The main goal of the present randomized clinical trial was to investigate the effects of subcutaneous administration of two different local anesthetics at trocar incision sites at the abdominal wall in combination with intraoperative intraperitoneal instillation of local anesthetics, on the character of postoperative pain, in adolescents who underwent laparoscopic varicocelectomy. Methods: A total of 60 patients with a median age of 16 years, who received laparoscopic varicocele repair, were included in this randomized clinical trial. The patients were randomly assigned to three study groups receiving 2% lidocaine, 0.5% levobupivacaine, or the control group. The Visual Analogue Scale (VAS) was used by a blinded nurse at four different time points (2, 6, 12 and 24 h after the surgery) to measure pain intensity. Results: The significant effect of time on the pain intensity (p = 0.001) was found. Additionally, the interaction between time and different local analgesics (p < 0.001) was observed. In patients in whom 0.5% levobupivacaine has been used, significantly lower VAS pain scores were recorded at each time point assessed, in comparison with the patients who received 2% lidocaine or the patients from the control group in whom no local anesthetic was applied (p < 0.001). Furthermore, in patients in whom 2% lidocaine was administrated, significantly lower pain levels according to VAS were reported than in those from the control group, except for the time point at 24 h after surgery when pain levels were comparable. Concerning the postoperative pain control, the number of patients who requested oral analgesics postoperatively was significantly lower in the group of patients in whom local anesthetic was administrated intraoperatively (2% lidocaine – n = 4, 20%; 0.5% levobupivacaine – n = 1, 5%) compared to the patients who did not receive any local anesthetic during the surgery (n = 13; 65%) (p < 0.001). Conclusion: A significant reduction in postoperative pain intensity and analgesics consumption in patients undergoing laparoscopic varicocelectomy who received intraoperative local anesthetic was observed. The best effect on postoperative pain intensity, according to the VAS score, was achieved by 0.5% levobupivacaine.

Bleeding Disorders – A Frequent Complication Related to the Use of Intrauterine Device with Low Dose Hormonal Mechanism of Action

2015 ◽  
Vol 638 ◽  
pp. 216-221 ◽  
Author(s):  
Monica Cîrstoiu ◽  
Catalin Cirstoiu ◽  
Iulian Vasile Antoniac ◽  
Octavian Munteanu
Keyword(s):  
Phase Ii ◽  
Mechanism Of Action ◽  
Adverse Reactions ◽  
Low Dose ◽  
Intrauterine Device ◽  
Bleeding Disorders ◽  
Frequent Complication ◽  
Hormonal Mechanism ◽  
Phase Ii And Iii

Due to fact that an intrauterine device with low dose hormonal mechanism of action - the 13.5 mg levonorgestrel-releasing intrauterine system has been just launched in Romania, the undesirable reactions have not been studied and reported. This system has a hormonal mechanism of action, releasing progesterone, with a particular delivering rate of levonorgestrel. Bleeding irregularities are among the very common adverse reactions reported by phase II and III studies. We performed this study in order to determine a profile of bleeding disorders after 2 months of therapy with the 13.5 mg levonorgestrel-releasing intrauterine system.

scholarly journals HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly

2021 ◽  
Author(s):  
Tina Yip ◽  
Jia Hu ◽  
Pamela S Hawn ◽  
Amy Yamamoto ◽  
Gary Oderda
Keyword(s):  
Clinical Trial ◽  
Postoperative Pain ◽  
Elderly Patients ◽  
Pain Intensity ◽  
Local Anesthetic ◽  
Extended Release ◽  
The Elderly ◽  
Opioid Consumption ◽  
Opioid Use ◽  
Clinical Trial Registration

Aim: HTX-011 (ZYNRELEF™) is an extended-release, dual-acting local anesthetic containing bupivacaine and meloxicam. In bunionectomy and herniorrhaphy studies, HTX-011 resulted in less postoperative pain and less opioid consumption versus bupivacaine HCl. Here we evaluate HTX-011 in patients aged ≥65 years. Materials & methods: Patients received placebo, bupivacaine HCl or HTX-011 following surgery. End points included pain intensity, total opioid consumption, opioid-free patients and safety. Results: HTX-011-treated patients reported lower postoperative pain through 72 h versus bupivacaine HCl and placebo. Elderly patients administered HTX-011 used fewer opioids versus bupivacaine HCl, and a greater proportion remained opioid-free through 72 h. HTX-011 was well tolerated with a safety profile similar to bupivacaine HCl and placebo. Conclusion: HTX-011 maintained effectiveness and was well tolerated in elderly patients. Clinical Trial Registration: NCT03295721 and NCT03237481

A randomized phase II trial of sorafenib versus sorafenib plus low-dose interferon-alfa: Clinical results and biomarker analysis

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 5093-5093 ◽  
Author(s):  
N. M. Tannir ◽  
A. J. Zurita ◽  
J. V. Heymach ◽  
H. T. Tran ◽  
L. C. Pagliaro ◽  
...  
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Clinical Results ◽  
Interferon Alfa ◽  
Randomized Phase Ii ◽  
Biomarker Analysis

scholarly journals Is lumbar erector spinae plane block (L-ESPB) a lumbar plexus block?: a case report of three cases

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Ashok Jadon ◽  
Rajendra Kumar Sahoo ◽  
Santosh Kumar Sharma
Keyword(s):  
Postoperative Pain ◽  
Mechanism Of Action ◽  
Local Anesthetic ◽  
Postoperative Pain Management ◽  
Erector Spinae ◽  
Lumbar Plexus ◽  
Anesthetic Technique ◽  
Erector Spinae Plane Block ◽  
Ionic Contrast ◽  
Plexus Block

Abstract Background Lumbar erector spinae plane block (L-ESPB) is being used in fractured hip patients for the postoperative pain relief and as a sole anesthetic technique. Various clinical and cadaveric studies have differences of opinion about its mechanism of action and pathways of local anesthetic spread; however, the role of lumbar plexus (LP) in the mechanism of action is still not considered. In our clinical experience, we observed that the action on LP could be a pathway for the analgesic action of local anesthetic along with paravertebral spread. Case presentation We report here three cases of the fractured hip who were given L-ESPB for postoperative pain management. The radiological examination was done after injection of non-ionic contrast to know the spread of local anesthetic. In two cases, the contrast spread was seen towards LP and in one case spread of contrast was observed towards the paravertebral area. Conclusions Effect of local anesthetic on the lumbar plexus is one of the plausible pathways in L-ESPB for its analgesic mechanism of action.

HTX-011 (bupivacaine and meloxicam) for the prevention of postoperative pain – clinical considerations

2021 ◽  
Author(s):  
Elyse M Cornett ◽  
Michelle A Carroll Turpin ◽  
Matthew Busby ◽  
Alex D Pham ◽  
Anusha Kallurkar ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Extended Release ◽  
Low Dose ◽  
Great Promise ◽  
Sodium Channel Blocker ◽  
Liposomal Bupivacaine ◽  
Analgesic Effects ◽  
Pain Scores ◽  
Surgical Recovery ◽  
Clinical Considerations

HTX-011 is an extended-release, dual-acting local anesthetic consisting of liposomal bupivacaine (sodium-channel blocker) and low-dose meloxicam (non-steroidal anti-inflammatory drug [NSAID]) applied needle-free during surgery. Introducing low-dose meloxicam addresses the limited efficacy of liposomal bupivacaine in acidic inflamed tissues and allows enhanced analgesic effects over three days. It has great promise to be an extremely effective postoperative pain regimen and produce an opioid-free surgical recovery, as it has consistently significantly reduced pain scores and opioid consumption through 72 h. This manuscript provides an updated, concise narrative review of the pharmacology, clinical efficacy, safety and tolerability of this drug and its applications to prevent postoperative pain.

216 Azacitidine low-dose schedule in low-risk myelodysplastic syndromes. Clinical results of a multicenter phase II study

2011 ◽  
Vol 35 ◽  
pp. S84-S85 ◽  
Author(s):  
C. Fill ◽  
C. Finelli ◽  
M. Gobbi ◽  
G. Martinelli ◽  
I. Iacobucci ◽  
...  
Keyword(s):  
Phase Ii ◽  
Myelodysplastic Syndromes ◽  
Low Dose ◽  
Phase Ii Study ◽  
Dose Schedule ◽  
Clinical Results ◽  
Low Risk ◽  
Multicenter Phase
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