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ABT ‐ 719 for the Prevention of Acute Kidney Injury in Patients Undergoing High ‐ Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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.

Methods and results: 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.

Conclusions: 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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

No MeSH data available.


Effect of ABT‐719 treatment on incidence of composite outcomes (MAKE). *Percentage of patients developing at least 1 of the composite events of death, needing RRT during the 90‐day postoperative period or ≥25% reduction in eGFR at day 90. eGFR indicates estimated glomerular filtration rate; MAKE, major adverse kidney events; RRT, renal replacement therapy. *95% CI for any composite event.
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jah31688-fig-0003: Effect of ABT‐719 treatment on incidence of composite outcomes (MAKE). *Percentage of patients developing at least 1 of the composite events of death, needing RRT during the 90‐day postoperative period or ≥25% reduction in eGFR at day 90. eGFR indicates estimated glomerular filtration rate; MAKE, major adverse kidney events; RRT, renal replacement therapy. *95% CI for any composite event.

Mentions: There were no significant differences in the percentage of patients who developed AKI among the treatment groups based on the RIFLE and KDIGO AKI scoring criteria (data not shown). Comparing the incidence of AKI using RIFLE and KDIGO criteria based on SCr only, urine output only, or both SCr and/or urine output did not alter the conclusion (Figure 2B through 2D). However, AKI incidence was relatively higher using the RIFLE criteria compared with KDIGO criteria because the RIFLE criteria include reduction in eGFR (Figure 2B and 2D). The efficacy of treatment with ABT‐719 was further assessed by comparing the percentage of patients who developed ≥1 of the 90‐day composite outcomes (MAKE). Overall, there was no significant difference between patients receiving placebo and ABT‐719 (P=0.250). Compared to the placebo group (n=12; 20.3%; 95% CI, 11.0–32.8), similar percentages of patients in the 800‐μg/kg group (n=7; 12.3%; 95% CI, 5.1–23.7), 1600‐μg/kg group (n=6; 10.2%; 95% CI, 3.8–20.8), and 2100‐μg/kg group (n=11; 19.6%; 95% CI, 10.2–32.4) developed a MAKE event (Figure 3). When events were examined individually, participants needed RRT across all ABT‐719 treatment groups (4 of 172; 2.3%) at a numerically lower, albeit not statistically significant, rate compared to patients in the placebo group (5 of 59; 8.5%; P=0.055; Figure 3).


ABT ‐ 719 for the Prevention of Acute Kidney Injury in Patients Undergoing High ‐ Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial
Effect of ABT‐719 treatment on incidence of composite outcomes (MAKE). *Percentage of patients developing at least 1 of the composite events of death, needing RRT during the 90‐day postoperative period or ≥25% reduction in eGFR at day 90. eGFR indicates estimated glomerular filtration rate; MAKE, major adverse kidney events; RRT, renal replacement therapy. *95% CI for any composite event.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5015281&req=5

jah31688-fig-0003: Effect of ABT‐719 treatment on incidence of composite outcomes (MAKE). *Percentage of patients developing at least 1 of the composite events of death, needing RRT during the 90‐day postoperative period or ≥25% reduction in eGFR at day 90. eGFR indicates estimated glomerular filtration rate; MAKE, major adverse kidney events; RRT, renal replacement therapy. *95% CI for any composite event.
Mentions: There were no significant differences in the percentage of patients who developed AKI among the treatment groups based on the RIFLE and KDIGO AKI scoring criteria (data not shown). Comparing the incidence of AKI using RIFLE and KDIGO criteria based on SCr only, urine output only, or both SCr and/or urine output did not alter the conclusion (Figure 2B through 2D). However, AKI incidence was relatively higher using the RIFLE criteria compared with KDIGO criteria because the RIFLE criteria include reduction in eGFR (Figure 2B and 2D). The efficacy of treatment with ABT‐719 was further assessed by comparing the percentage of patients who developed ≥1 of the 90‐day composite outcomes (MAKE). Overall, there was no significant difference between patients receiving placebo and ABT‐719 (P=0.250). Compared to the placebo group (n=12; 20.3%; 95% CI, 11.0–32.8), similar percentages of patients in the 800‐μg/kg group (n=7; 12.3%; 95% CI, 5.1–23.7), 1600‐μg/kg group (n=6; 10.2%; 95% CI, 3.8–20.8), and 2100‐μg/kg group (n=11; 19.6%; 95% CI, 10.2–32.4) developed a MAKE event (Figure 3). When events were examined individually, participants needed RRT across all ABT‐719 treatment groups (4 of 172; 2.3%) at a numerically lower, albeit not statistically significant, rate compared to patients in the placebo group (5 of 59; 8.5%; P=0.055; Figure 3).

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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.

Methods and results: 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.

Conclusions: 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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

No MeSH data available.