A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)
Institution:
1. Nicklaus Children''s Hospital, Miami, FL, United States of America;2. University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America;3. Indiana University School of Medicine, Indianapolis, IN, United States of America;4. Stanford University School of Medicine, Stanford, CA, United States of America;5. Shriners Hospital for Children, Chicago, IL, United States of America;6. University of Texas, McGovern Medical School, Houston, TX, United States of America;7. Pacira BioSciences, Inc., Parsippany, NJ, United States of America;8. Lyndra Therapeutics, Watertown, MA, United States of America;9. Cleveland Clinic, Cleveland, OH, United States of America
Abstract:
Study objectiveTo evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.DesignMulticenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).SettingOperating room.PatientsTwo separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).InterventionRandomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).MeasurementsThe primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively.Main resultsBaseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% 19/31]) and bupivacaine HCl (73% 22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.ConclusionsPlasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000–4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302
