title: ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial.
abstract: Patients undergoing cardiac surgeries with cardiopulmonary bypass (on-pump) have a high risk for acute kidney injury (AKI). We tested ABT-719, a novel α-melanocyte-stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.
  
  
  
  This phase 2b randomized, double-blind, placebo-controlled trial included adult patients with stable renal function undergoing high-risk on-pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT-719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72-hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800-, 1600-, and 2100-μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair-wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.
  
  
  
  ABT-719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90-day outcomes in patients after cardiac surgery.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.
authors.affiliation: Texas A&M, Department of Internal Medicine Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX The Heart Hospital, Plano, TX peteramccullough@gmail.com.
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
authors.affiliation: Stony Brook Medicine Health Science Center, Stony Brook, NY.
authors.forename: Elliott
authors.initials: E
authors.lastname: Bennett-Guerrero
authors.affiliation: George Washington School of Medicine, Department of Internal Medicine, Veterans Affairs Medical Center, Washington, DC.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, FL.
authors.forename: Thomas
authors.initials: T
authors.lastname: Beaver
authors.affiliation: Department of Internal Medicine, University of California San Diego Medical Center, San Diego, CA.
authors.forename: Ravindra L
authors.initials: RL
authors.lastname: Mehta
authors.affiliation: Department of Internal Medicine, Indiana University, Indianapolis, IN.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.affiliation: Renal Clinical Development, AbbVie Inc., North Chicago, IL.
authors.forename: Ann
authors.initials: A
authors.lastname: Eldred
authors.affiliation: Statistics, AbbVie Inc., North Chicago, IL.
authors.forename: Greg
authors.initials: G
authors.lastname: Ball
authors.affiliation: Statistics, AbbVie Inc., North Chicago, IL.
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Renal Clinical Development, AbbVie Inc., North Chicago, IL.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Houser
authors.affiliation: Renal Clinical Development, AbbVie Inc., North Chicago, IL.
authors.forename: Samina
authors.initials: S
authors.lastname: Khan
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003422:Critical Care / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D061214:Patient Safety; D011183:Postoperative Complications / Q000517:prevention & control; D011728:Pyridones / Q000627:therapeutic use; D012076:Renal Agents / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011728:Pyridones; D012076:Renal Agents; C093440:ABT 719
keywords: acute kidney injury; cardiopulmonary bypass; clinical trial; kidney; renal; renal function; α‐melanocyte‐stimulating hormone