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

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT01777165

Collaborator

(none)

240

Enrollment

Locations

Arms

12.9

Duration (Months)

5.9

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Drug: ABT-719 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 ABT-719 lower dose	Drug: ABT-719 1 arm of ABT-719 higher dose, 1 arm of ABT-719 intermediate dose, and 1 arm ABT-719 lower dose
Experimental: Arm 2 ABT-719 intermediate dose	Drug: ABT-719 1 arm of ABT-719 higher dose, 1 arm of ABT-719 intermediate dose, and 1 arm ABT-719 lower dose
Experimental: Arm 3 ABT-719 higher dose	Drug: ABT-719 1 arm of ABT-719 higher dose, 1 arm of ABT-719 intermediate dose, and 1 arm ABT-719 lower dose
Placebo Comparator: Arm 4 placebo	Drug: Placebo Placebo infusion

Outcome Measures

Primary Outcome Measures

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. [Up through Day 7]

Secondary Outcome Measures

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 [Up through Day 90]
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) [Up through Day 60]
Proportion of subjects developing AKI as defined by the Risk, Injury, Failure, Loss, or ESRD (RIFLE) model [Up through Day 7]
Proportion of subjects developing AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) model [Up through Day 7]
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 [Up through Day 90]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 83739	Danbury	Connecticut	United States	06810
2	Site Reference ID/Investigator# 87720	Gainesville	Florida	United States	32610
3	Site Reference ID/Investigator# 83746	Jacksonville	Florida	United States	32207
4	Site Reference ID/Investigator# 83733	Jacksonville	Florida	United States	32216
5	Site Reference ID/Investigator# 89178	Tampa	Florida	United States	33613
6	Site Reference ID/Investigator# 87693	Atlanta	Georgia	United States	30322
7	Site Reference ID/Investigator# 87717	Augusta	Georgia	United States	30912
8	Site Reference ID/Investigator# 89180	Fort Wayne	Indiana	United States	46804
9	Site Reference ID/Investigator# 101942	Indianapolis	Indiana	United States	46237
10	Site Reference ID/Investigator# 85917	Lexington	Kentucky	United States	40536
11	Site Reference ID/Investigator# 83732	Bethesda	Maryland	United States	20814
12	Site Reference ID/Investigator# 83724	Boston	Massachusetts	United States	02115
13	Site Reference ID/Investigator# 83745	Boston	Massachusetts	United States	02135
14	Site Reference ID/Investigator# 83750	Grand Blanc	Michigan	United States	48439
15	Site Reference ID/Investigator# 83747	Petoskey	Michigan	United States	49770
16	Site Reference ID/Investigator# 83744	Royal Oak	Michigan	United States	48073
17	Site Reference ID/Investigator# 85913	Saint Paul	Minnesota	United States	55102
18	Site Reference ID/Investigator# 96455	Saint Louis	Missouri	United States	63131
19	Site Reference ID/Investigator# 91253	Omaha	Nebraska	United States	68198-2315
20	Site Reference ID/Investigator# 93673	Newark	New Jersey	United States	07102
21	Site Reference ID/Investigator# 83722	New York	New York	United States	10032
22	Site Reference ID/Investigator# 89176	Asheville	North Carolina	United States	28803
23	Site Reference ID/Investigator# 83723	Durham	North Carolina	United States	27710
24	Site Reference ID/Investigator# 92413	Gastonia	North Carolina	United States	28054
25	Site Reference ID/Investigator# 87733	Winston-Salem	North Carolina	United States	27103
26	Site Reference ID/Investigator# 83735	Cincinnati	Ohio	United States	45219
27	Site Reference ID/Investigator# 91813	Columbus	Ohio	United States	43210
28	Site Reference ID/Investigator# 83738	Toledo	Ohio	United States	43606
29	Site Reference ID/Investigator# 91693	Portland	Oregon	United States	97225
30	Site Reference ID/Investigator# 89182	Springfield	Oregon	United States	97447
31	Site Reference ID/Investigator# 83734	Pittsburgh	Pennsylvania	United States	15232
32	Site Reference ID/Investigator# 83730	Knoxville	Tennessee	United States	37923
33	Site Reference ID/Investigator# 101876	Memphis	Tennessee	United States	38120
34	Site Reference ID/Investigator# 90614	Charlottesville	Virginia	United States	22908
35	Site Reference ID/Investigator# 83725	Richmond	Virginia	United States	23225
36	Site Reference ID/Investigator# 87714	Tacoma	Washington	United States	98405
37	Site Reference ID/Investigator# 91814	Madison	Wisconsin	United States	53792
38	Site Reference ID/Investigator# 87739	Milwaukee	Wisconsin	United States	53215
39	Site Reference ID/Investigator# 94956	Aarhus N		Denmark	DK-8200
40	Site Reference ID/Investigator# 109295	Copenhagen O		Denmark	2100
41	Site Reference ID/Investigator# 94955	Odense C		Denmark	5000