Browsing by Author "Scranton, Richard"

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    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)
    (Elsevier, 2021) Tirotta, Christopher F.; de Armendi, Alberto J.; Horn, Nicole D.; Hammer, Gregory B.; Szczodry, Michal; Matuszczak, Maria; Wang, Natalie Q.; Scranton, Richard; Ballock, Robert Tracy; Anesthesia, School of Medicine
    Study objective: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Design: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). Setting: Operating room. Patients: Two 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). Intervention: Randomized 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). Measurements: The 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 results: Baseline 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. Conclusions: Plasma 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.
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    Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations
    (International Association for the Study of Pain, 2021) Gewandter, Jennifer S.; Smith, Shannon M.; Dworkin, Robert H.; Turk, Dennis C.; Gan, Tong Joo; Gilron, Ian; Hertz, Sharon; Katz, Nathaniel P.; Markman, John D.; Raja, Srinivasa N.; Rowbotham, Michael C.; Stacey, Brett R.; Strain, Eric C.; Ward, Denham S.; Farrar, John T.; Kroenke, Kurt; Rathmell, James P.; Rauck, Richard; Brown, Colville; Cowan, Penney; Edwards, Robert R.; Eisenach, James C.; Ferguson, McKenzie; Freeman, Roy; Gray, Roy; Giblin, Kathryn; Grol-Prokopczyk, Hanna; Haythornthwaite, Jennifer; Jamison, Robert N.; Martel, Marc; McNicol, Ewan; Oshinsky, Michael; Sandbrink, Friedhelm; Scholz, Joachim; Scranton, Richard; Simon, Lee S.; Steiner, Deborah; Verburg, Kenneth; Wasan, Ajay D.; Wentworth, Kerry; Medicine, School of Medicine
    Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.