PMID- 28025372
OWN - NLM
STAT- MEDLINE
DCOM- 20171003
LR  - 20180711
IS  - 1526-4637 (Electronic)
IS  - 1526-2375 (Linking)
VI  - 17
IP  - 12
DP  - 2016 Dec
TI  - A Pooled Analysis Evaluating Renal Safety in Placebo- and Active 
      Comparator-Controlled Phase III Trials of Multiple-Dose Injectable 
      HPbetaCD-Diclofenac in Subjects with Acute Postoperative Pain.
PG  - 2378-2388
LID - 10.1093/pm/pnw146 [doi]
AB  - 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 
      HPbetaCD-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 HPbetaCD-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 HPbetaCD-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 HPbetaCD-diclofenac) was treatment-related. One incidence of 
      postoperative shift to high (> upper limit of normal) serum creatinine occurred 
      in the HPbetaCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in 
      serum creatinine or BUN did not differ significantly between patients receiving 
      HPbetaCD-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 HPbetaCD-diclofenac use for acute postoperative pain may not be 
      associated with added renal safety risks over placebo in this patient population.
CI  - (c) 2016 American Academy of Pain Medicine. All rights reserved. For permissions, 
      please e-mail: journals.permissions@oup.com.
FAU - Daniels, Stephen E
AU  - Daniels SE
AD  - *Premier Research, Austin, Texas.
FAU - Gan, Tong J Tj
AU  - Gan TJ
AD  - Department of Anesthesiology, Stony Brook University, Stony Brook, New York.
FAU - Hamilton, Douglas A
AU  - Hamilton DA
AD  - Javelin Pharmaceuticals, Inc. (now Hospira), a Pfizer Company, Lake Forest, 
      Illinois.
AD  - New Biology Ventures LLC, San Mateo, California.
FAU - Singla, Neil
AU  - Singla N
AD  - Lotus Clinical Research, LLC, Pasadena, California.
FAU - Lacouture, Peter G
AU  - Lacouture PG
AD  - Magidom Discovery, LLC, St. Augustine, Florida.
AD  - Brown University School of Medicine, Providence, Rhode Island.
FAU - Johnson, Olufunmibi
AU  - Johnson O
AD  - **Hospira, a Pfizer Company, Lake Forest, Illinois.
FAU - Min, Lauren H
AU  - Min LH
AD  - **Hospira, a Pfizer Company, Lake Forest, Illinois.
FAU - Reyes, Christian R D
AU  - Reyes CR
AD  - **Hospira, a Pfizer Company, Lake Forest, Illinois.
FAU - Carr, Daniel B
AU  - Carr DB
AD  - Javelin Pharmaceuticals, Inc. (now Hospira), a Pfizer Company, Lake Forest, 
      Illinois daniel.carr@tufts.edu.
AD  - Department of Anesthesiology, Tufts Medical Center, Boston, Massachusetts, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160717
PL  - England
TA  - Pain Med
JT  - Pain medicine (Malden, Mass.)
JID - 100894201
RN  - 0 (Analgesics)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (beta-Cyclodextrins)
RN  - 144O8QL0L1 (Diclofenac)
RN  - 1I96OHX6EK (2-Hydroxypropyl-beta-cyclodextrin)
SB  - IM
MH  - 2-Hydroxypropyl-beta-cyclodextrin
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Analgesics/administration & dosage/adverse effects
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/*adverse effects
MH  - Diclofenac/*administration & dosage/*adverse effects
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Kidney/*drug effects
MH  - Male
MH  - Middle Aged
MH  - Pain, Postoperative/*drug therapy
MH  - Young Adult
MH  - beta-Cyclodextrins/administration & dosage/adverse effects
OTO - NOTNLM
OT  - Acute Pain
OT  - Diclofenac
OT  - NSAID
OT  - Pain Management
OT  - Renal
OT  - Safety
EDAT- 2016/12/28 06:00
MHDA- 2017/10/04 06:00
CRDT- 2016/12/28 06:00
PHST- 2016/12/28 06:00 [entrez]
PHST- 2016/12/28 06:00 [pubmed]
PHST- 2017/10/04 06:00 [medline]
AID - pnw146 [pii]
AID - 10.1093/pm/pnw146 [doi]
PST - ppublish
SO  - Pain Med. 2016 Dec;17(12):2378-2388. doi: 10.1093/pm/pnw146. Epub 2016 Jul 17.