Study of Roxadustat for Reducing the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting

Study Overview
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Brief Summary
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Acute kidney injury is a frequent complication after coronary artery bypass grafting (CABG). Roxadustat is a prolyl hydroxylase inhibitor (PHI) which can stabilize hypoxia-inducible factor (HIF) and improve the hypoxic tolerance of tissues. Roxadustat has shown effect in reducing acute kidney injury in animal studies. This study aims to evaluate the efficacy of administration of Roxadustat before surgery in the prevention of acute kidney injury after CABG.

Detailed Description
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Acute kidney injury is a frequent complication after coronary artery bypass grafting (CABG), with a incidence of 28-38%. Renal ischemia-reperfusion injury is the main mechanism for acute kidney injury after CABG. Roxadustat is a kind of prolyl hydroxylase inhibitor (PHI) which can stabilize hypoxia-inducible factor (HIF) and improve the hypoxic tolerance of tissues. Roxadustat has shown effect in reducing acute kidney injury in animal studies. This study aims to evaluate the efficacy of administration of Roxadustat (before surgery) in the prevention of acute kidney injury after CABG. This is a multicenter, randomized, double-blind, placebo-controlled study.

Official Title
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Roxadustat Reduces the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting: a Multicenter, Randomized, Double-blind, Placebo-controlled Study

Conditions
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Coronary Artery Bypass

Intervention / Treatment
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* Drug: Roxadustat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years old non-emergent CABG and planned cardiopulmonary bypass (CPB) eGFR>15ml/min/1.73m2 Exclusion Criteria: pregnancy or breast feeding malignancy severe liver dysfunction acute kidney injury before randomization uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roxadustat<br>Roxadustat | Drug: Roxadustat<br>* orally 100mg every other day for 5-8 days prior to CABG<br>* Other names: Evrenzo;|
| Placebo Comparator: placebo<br>Placebo has the same appearance with the experimental drug (Roxadustat). | Drug: Placebo<br>* orally 100mg every other day for 5-8 days prior to CABG<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute kidney injury | elevation of serum creatinine ≥0.3mg/dl（26.5μmol/L）or ≥ 1.5 times baseline levels within 48 hours post surgery | 0-48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| classification of acute kidney injury | classification of of acute kidney injury based on AKIN criteria | 0-3 days after surgery | 
| renal function | creatinine, urea, Cystatin-C after surgery | 0-3 days after surgery | 
| new biomarkers of renal injury | serum and urine NGAL，urine TIMP2*IGFBP7 | immediately after surgery and the first morning after surgery | 
| Cardiac Troponin Subunit I (cTnI) | peak plasma concentration of cTnI and area under curve (AUC) of cTnI | 0-3 days after surgery | 
| brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) | plasma concentration of BNP | 0-3 days after surgery | 
| death | death during hospitalization | through study completion, an average of one month | 
| length of hospital stay and ICU stay | length of hospital stay and ICU stay | through study completion, an average of one month | 
| Blood infusion | amount of Red blood cells infusion after surgery | 0-3 days after surgery | 
| adverse events | adverse events and severe adverse events during hospitalization | through study completion, an average of one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute kidney injury, coronary artery bypass, Roxadustat