E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10069339 |
E.1.2 | Term | Acute kidney injury |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study objective is to compare the safety and efficacy of doses of 800 mcg/kg, 1600 mcg/kg and 2100 mcg/kg intravenous (IV) infusions of ABT-719 to placebo in subjects who are at risk of AKI and undergoing pre-defined on-pump cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. subject must be male or female, age >= 18 years old
2. subjects must have stable renal function per Investigator discretion and no known change in serum creatinine of >= 0.3 mg during preceding 4 weeks.
3. subjects with eGFR less than or equal to 60 mL/min/1.73m2 who require intravascular iodinated contrast within 48 hours of the day of surgery, will only be included if no known serum creatinine change >= 0.3 mg.
4. subjects must be undergoing a pre-defined on-pump cardiac surgery
meeting one of the following AKI risk factors:
a. Subjects is undergoing combined coronary artery bypass grafting surgery and surgery
of one or more cardiac valve or
b. Subject is undergoing sugery of more than one cardiac valve or
c. subject is undergoing surgery of the aortic root or ascending part of the aorta or
d. subject is undergoing surgery of the aortic root or ascending part of the aorta,
combined with CABG and/or valve(s) surgery or
e. Subject has an eGFR >= 16 mL/min/1.73m2 and <=59 mL/min/1.73m2 as determined by
CKD-EPI formula at Screenin, and is undergoing CABG or single valve surgery. |
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E.4 | Principal exclusion criteria |
1. Has an eGFR less than or equal to 15 mL/min/1.73m2
2. Cardiac surgery without cardiopulmonary bypass
3. Has ongoing sepsis or history of sepsis within the last 2 weeks or untreated diagnosed infection prior to Screening visit
4. Has known/documented history of RIFLE "R" or AKIN "Stage I" within the previous 4 weeks
5. Recently received (within the last 10 weeks) or is anticipated to receive chemotherapy which can interfere with kidney function |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects developing AKI as defined by the AKIN scoring criteria (Stage 1, Stage 2, or Stage 3) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
proportion of subjects developing at least one of the composite events:
death, needing RRT during the 90 day post-operative peroid, or having a >= 25% reduction in eGFR or measured GfR at Day 90 post-surgery visit
porportion of subjects developing at least one of the composite events: death, needing RRT during the 60 day post-operative period, or
having a >=25% reduction in eGFR or measured GFR at Day 60 post-surgery visit
proportion of subjects developing AKI as defined by the RIFLE scoring criteria
proportion of subjects developing AKI as defined by the KDIGO scoring criteria
changes from baseline in serum creatinine and S-Cystatin C at all study visits from Day 0 to Day 90
maximal change from baseline in SCr and S-Cystatin C until Day 7 or until discharge from the hospital
changes from baseline in eGFR and measured GFR at all study visits from Day 0 to Day 90
changes from baseline in AKI biomarkers (urine and serum) at all study visits from Day 0 to Day 90
maximal change from baseline in AKI biomarkers over a 72 hour period after clamp release
number of hospitalizations and days hospitalized during the 90 day post-operative period
Eq-5D endpoints |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |