title: Design of clinical trials in AKI: a report from an NIDDK workshop. Trials of patients with sepsis and in selected hospital settings.
abstract: AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients.
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, IN, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Paul M
authors.initials: PM
authors.lastname: Palevsky
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.forename: James S
authors.initials: JS
authors.lastname: Kaufman
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Robert M
authors.initials: RM
authors.lastname: Toto
authors.forename: Chi-yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Tom H
authors.initials: TH
authors.lastname: Greene
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Faubel
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: Ron
authors.initials: R
authors.lastname: Wald
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Murray
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shaw
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Cheung
authors.forename: Steven D
authors.initials: SD
authors.lastname: Weisbord
authors.forename: Ravindra L
authors.initials: RL
authors.lastname: Mehta
authors.forename: John B
authors.initials: JB
authors.lastname: Stokes
authors.forename: Aliza M
authors.initials: AM
authors.lastname: Thompson
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: Christof S
authors.initials: CS
authors.lastname: Westenfelder
authors.forename: James A
authors.initials: JA
authors.lastname: Tumlin
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.forename: Sudhir V
authors.initials: SV
authors.lastname: Shah
authors.forename: Yining
authors.initials: Y
authors.lastname: Xie
authors.forename: Emily G
authors.initials: EG
authors.lastname: Duggan
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods*; D003422:Critical Care; D016638:Critical Illness; D023381:Endpoint Determination; D006801:Humans; D007258:Informed Consent; D018579:Patient Selection; D011184:Postoperative Period; D018805:Sepsis / Q000150:complications*; D012720:Severity of Illness Index; D014947:Wounds and Injuries / Q000150:complications