Clinical trial NCT01777165: A Safety and Efficacy Trial of Multiple Dosing Regimens of ABT-719 for the Prevention of Acute Kidney Injury in Subjects Undergoing High Risk Cardiac Surgery
Official title: A Phase 2b, Randomized, Double-Blind,Placebo-Controlled, Safety and Efficacy Trial of Multiple Dosing Regimens of ABT-719 for the Prevention of Acute Kidney Injury in Subjects Undergoing High Risk Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: GFR
Acute Kidney Injury
High Risk cardiac surgery
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-01-28
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the safety and efficacy of ABT-719 in preventing acute kidney injury in patients undergoing high risk cardiac surgery.


Eligibility criteria: Inclusion Criteria:

* Subject must be male or female, age greater than or equal to 18 years old.
* Subjects must have stable renal function, per Investigator discretion and no known increase in serum creatinine of greater than or equal to 0.3 mg during the preceding 4 weeks.
* Subjects with estimated glomerular filtration rate less than or equal to 60 mL/min/1.73 m2 who require intravascular iodinated contrast within 48 hours of the day of surgery, will only be included if there is no known serum creatinine increase greater than or equal to 0.3 mg.
* Subjects must be undergoing a pre-defined on-pump cardiac surgery meeting one of the following acute kidney injury risk factors:
* Subject is undergoing combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery), or
* Subject is undergoing surgery of more than one cardiac valve (valves surgery), or
* Subject is undergoing surgery of the aortic root or ascending part of the aorta, or
* Subject is undergoing surgery of the aortic root or ascending part of the aorta, combined with coronary artery bypass graft and/or valve(s) surgery, or
* Subject has an estimated glomerular filtration rate greater than or equal to 16 mL/min/1.73 m2 and less than or equal to 59 mL/min/1.73 m2 as determined by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula at Screening, and is undergoing coronary artery bypass graft or single valve surgery.

Exclusion Criteria:

* Has an eGFR less than or equal to 15 mL/min/1.73 m2.
* Cardiac surgery to be performed without cardiopulmonary bypass.
* Has ongoing sepsis or history of sepsis within the last 2 weeks or untreated diagnosed infection prior to Screening visit. Sepsis is defined as presence of a confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension.
* Has known or documented RIFLE "R" or AKIN "Stage I" within the previous 4 weeks.
* Recently received (within the last 10 weeks) or is anticipated to receive chemotherapy which can interfere with kidney function

Primary outcomes:
measure: Number of patients developing acute kidney injury based on the Acute Kidney Injury Network (AKIN) scoring criteria by comparing the ABT-719 dose groups versus placebo group.
timeFrame: Up through Day 7
Secondary outcomes:
measure: Proportion of subjects developing at least one of the composite events: death, needing renal replacement therapy, or having greater than or equal to 25 percent reduction in estimated glomerular filtration rate or measured glomerular filtration rate
timeFrame: Up through Day 90
measure: Proportion of subjects developing at least one of the composite events: death, needing renal replacement therapy, or having greater than or equal to 25 percent reduction in serum creatinine based estimated glomerular filtration rate (GFR)
timeFrame: Up through Day 60
measure: Proportion of subjects developing AKI as defined by the Risk, Injury, Failure, Loss, or ESRD (RIFLE) model
timeFrame: Up through Day 7
measure: Proportion of subjects developing AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) model
timeFrame: Up through Day 7
measure: Changes from baseline (defined as within 24 hours of day 0) in serum creatinine (SCr) and S-Cystatin C at all study visits from baseline to Day 90
timeFrame: Up through Day 90
Other outcomes:
Locations:
city: Danbury
country: United States
facility: Site Reference ID/Investigator# 83739
state: Connecticut
city: Gainesville
country: United States
facility: Site Reference ID/Investigator# 87720
state: Florida
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 83746
state: Florida
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 83733
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 89178
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 87693
state: Georgia
city: Augusta
country: United States
facility: Site Reference ID/Investigator# 87717
state: Georgia
city: Fort Wayne
country: United States
facility: Site Reference ID/Investigator# 89180
state: Indiana
city: Indianapolis
country: United States
facility: Site Reference ID/Investigator# 101942
state: Indiana
city: Lexington
country: United States
facility: Site Reference ID/Investigator# 85917
state: Kentucky
city: Bethesda
country: United States
facility: Site Reference ID/Investigator# 83732
state: Maryland
city: Boston
country: United States
facility: Site Reference ID/Investigator# 83724
state: Massachusetts
city: Boston
country: United States
facility: Site Reference ID/Investigator# 83745
state: Massachusetts
city: Grand Blanc
country: United States
facility: Site Reference ID/Investigator# 83750
state: Michigan
city: Petoskey
country: United States
facility: Site Reference ID/Investigator# 83747
state: Michigan
city: Royal Oak
country: United States
facility: Site Reference ID/Investigator# 83744
state: Michigan
city: Saint Paul
country: United States
facility: Site Reference ID/Investigator# 85913
state: Minnesota
city: Saint Louis
country: United States
facility: Site Reference ID/Investigator# 96455
state: Missouri
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 91253
state: Nebraska
city: Newark
country: United States
facility: Site Reference ID/Investigator# 93673
state: New Jersey
city: New York
country: United States
facility: Site Reference ID/Investigator# 83722
state: New York
city: Asheville
country: United States
facility: Site Reference ID/Investigator# 89176
state: North Carolina
city: Durham
country: United States
facility: Site Reference ID/Investigator# 83723
state: North Carolina
city: Gastonia
country: United States
facility: Site Reference ID/Investigator# 92413
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 87733
state: North Carolina
city: Cincinnati
country: United States
facility: Site Reference ID/Investigator# 83735
state: Ohio
city: Columbus
country: United States
facility: Site Reference ID/Investigator# 91813
state: Ohio
city: Toledo
country: United States
facility: Site Reference ID/Investigator# 83738
state: Ohio
city: Portland
country: United States
facility: Site Reference ID/Investigator# 91693
state: Oregon
city: Springfield
country: United States
facility: Site Reference ID/Investigator# 89182
state: Oregon
city: Pittsburgh
country: United States
facility: Site Reference ID/Investigator# 83734
state: Pennsylvania
city: Knoxville
country: United States
facility: Site Reference ID/Investigator# 83730
state: Tennessee
city: Memphis
country: United States
facility: Site Reference ID/Investigator# 101876
state: Tennessee
city: Charlottesville
country: United States
facility: Site Reference ID/Investigator# 90614
state: Virginia
city: Richmond
country: United States
facility: Site Reference ID/Investigator# 83725
state: Virginia
city: Tacoma
country: United States
facility: Site Reference ID/Investigator# 87714
state: Washington
city: Madison
country: United States
facility: Site Reference ID/Investigator# 91814
state: Wisconsin
city: Milwaukee
country: United States
facility: Site Reference ID/Investigator# 87739
state: Wisconsin
city: Aarhus N
country: Denmark
facility: Site Reference ID/Investigator# 94956
city: Copenhagen O
country: Denmark
facility: Site Reference ID/Investigator# 109295
city: Odense C
country: Denmark
facility: Site Reference ID/Investigator# 94955
Study officials:
affiliation: AbbVie
name: Ann Eldred, MD
role: STUDY_DIRECTOR
References:
citation: McCullough PA, Bennett-Guerrero E, Chawla LS, Beaver T, Mehta RL, Molitoris BA, Eldred A, Ball G, Lee HJ, Houser MT, Khan S. ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial. J Am Heart Assoc. 2016 Aug 20;5(8):e003549. doi: 10.1161/JAHA.116.003549.