Hepatocyte Growth Factor Mimetic ANG-3777 for Cardiac Surgery–Associated Acute Kidney Injury
| Autor: | John F. Neylan, Sabry Ayad, Madhav Swaminathan, Deborah Gouveia, Tracy J. Mayne |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
030232 urology & nephrology Renal function 030204 cardiovascular system & hematology law.invention Nephrotoxicity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law Clinical Research Cardiopulmonary bypass medicine Renal replacement therapy Creatinine business.industry Acute kidney injury clinical trial medicine.disease Transplantation hepatocyte growth factor chemistry acute kidney injury Nephrology Anesthesia business cardiopulmonary bypass Reperfusion injury ANG-3777 cardiac surgery |
| Zdroj: | Kidney International Reports |
| ISSN: | 2468-0249 |
| Popis: | Introduction Nearly one-third of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB) experience cardiac surgery–associated (CSA) acute kidney injury (AKI); 5% require renal replacement therapy. ANG-3777 is a hepatocyte growth factor mimetic. In vitro, ANG-3777 reduces apoptosis and increases cell proliferation, migration, morphogenesis, and angiogenesis in injured kidneys. In animal models, ANG-3777 mitigates the effects of renal damage secondary to ischemia reperfusion injury and nephrotoxic chemicals. Phase 2 data in AKI of renal transplantation have shown improved renal function and comparable safety relative to placebo. The Guard Against Renal Damage (GUARD) study is a phase 2 proof of concept trial of ANG-3777 in CSA-AKI. Methods GUARD is a 240-patient, multicenter, double-blind, randomized placebo-controlled trial to assess the efficacy and safety of ANG-3777 in patients at elevated pre-surgery risk for AKI undergoing coronary artery bypass graft (CABG) or heart valve repair/replacement requiring CPB. Subjects are randomized 1:1 to receive ANG-3777 (2 mg/kg) or placebo. Study drug is dosed via 4 daily intravenous 30-minute infusions. The first dose is administered less than 4 hours after completing CPB, second at 24 ± 2 hours post-CPB, with two subsequent doses at 24 ± 2 hours after the previous dose. Results The primary efficacy endpoint is percent change from baseline serum creatinine to mean area under the curve from days 2 through 6. Secondary endpoints include change in estimated glomerular filtration rate from baseline to day 30, the proportion of patients diagnosed with AKI by stage through day 5, and the length of CSA-AKI hospitalization. Safety will include adverse events and laboratory measures. Conclusion This phase 2 study of ANG-3777 provides data to develop a phase 3 registrational study in this medically complex condition. Graphical abstract |
| Databáze: | OpenAIRE |
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