title: Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.
abstract: Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
authors.affiliation: Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Palevsky
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Ron
authors.initials: R
authors.lastname: Wald
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
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: Sarah G
authors.initials: SG
authors.lastname: Faubel
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
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: 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
authors.initials: T
authors.lastname: Greene
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 / Q000175:diagnosis* / Q000628:therapy*; D015415:Biomarkers; D002986:Clinical Trials as Topic / Q000379:methods*; D023381:Endpoint Determination; D005240:Feasibility Studies; D006801:Humans; D018579:Patient Selection; D010865:Pilot Projects; D018401:Sample Size; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers