A Pooled Analysis Evaluating Renal Safety in Placebo-and Active Comparator-Controlled Phase III Trials of Multiple-Dose Injectable HP beta CD-Diclofenac in Subjects with Acute Postoperative Pain

作者：Daniels Stephen E; Gan Tong J; Hamilton Douglas A; Singla Neil; Lacouture Peter G; Johnson Olufunmibi; Min Lauren H; Reyes Christian R D; Carr Daniel B^*

来源：Pain Medicine, 2016, 17(12): 2378-2388.

DOI：10.1093/pm/pnw146

• Acute Pain
• NSAID
• Pain Management
• Safety
• Diclofenac
• Renal

Objective. While injectable nonsteroidal anti-inflammatory drugs (NSAIDs) are a key component of postoperative multimodal analgesia, renal safety concerns may limit use in some patients. This study examined the renal safety of injectable HP beta CD-diclofenac when given for <= 5 days following orthopedic or abdominal/pelvic surgery.
Methods. Pooled analysis of data from two randomized, placebo- and active comparator-controlled phase III trials in 608 total patients was conducted. Renal safety was assessed by examining treatmentemergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts.
Results. There were three renal AEs each in the HP beta CD-diclofenac (n=318 patients) and placebo (n=148 patients) groups, and two renal AEs in the ketorolac group (n5142 patients). No significant difference in renal AE risk was detected for patients receiving HP beta CD-diclofenac (RR: 1.40 [0.15,13.3]; P=0.75) or ketorolac (RR: 2.08 [0.19,22.7]; P=0.56) versus placebo. All renal AEs were mild or moderate in severity, and a single renal AE (acute renal failure in a patient receiving HP beta CD-diclofenac) was treatment-related. One incidence of postoperative shift to high (>upper limit of normal) serum creatinine occurred in the HPbCD-diclofenac group (n=2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPbCD-diclofenac and placebo.
Conclusions. While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function, the results suggest that HPbCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.

• 出版日期2016-12