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

• Published in: Pain medicine (Malden, Mass.) Mass.), 2016-12, Vol.17 (12), p.2378-2388
• Main Authors: Daniels, Stephen E., Gan, Tong J. (TJ), Hamilton, Douglas A., Singla, Neil, Lacouture, Peter G., Johnson, Olufunmibi, Min, Lauren H., Reyes, Christian R. D., Carr, Daniel B.
• Format: Article
• Language: English
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1093/pm/pnw146

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 HPβCD-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 treatment-emergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts. Results. There were three renal AEs each in the HPβCD-diclofenac (n = 318 patients) and placebo (n = 148 patients) groups, and two renal AEs in the ketorolac group (n = 142 patients). No significant difference in renal AE risk was detected for patients receiving HPβCD-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 HPβCD-diclofenac) was treatment-related. One incidence of postoperative shift to high (> upper limit of normal) serum creatinine occurred in the HPβCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-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 HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.