Clinical trial NCT05010460: Study of Roxadustat for Reducing the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting
Official title: Roxadustat Reduces the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting: a Multicenter, Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Coronary Artery Bypass
Keywords: acute kidney injury
coronary artery bypass
Roxadustat
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Hospital
First posted: 2021-08-18
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: acute kidney injury
timeFrame: 0-48 hours after surgery
Secondary outcomes:
measure: classification of acute kidney injury
timeFrame: 0-3 days after surgery
measure: renal function
timeFrame: 0-3 days after surgery
measure: new biomarkers of renal injury
timeFrame: immediately after surgery and the first morning after surgery
measure: Cardiac Troponin Subunit I (cTnI)
timeFrame: 0-3 days after surgery
measure: brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP)
timeFrame: 0-3 days after surgery
measure: death
timeFrame: through study completion, an average of one month
measure: length of hospital stay and ICU stay
timeFrame: through study completion, an average of one month
measure: Blood infusion
timeFrame: 0-3 days after surgery
measure: adverse events
timeFrame: through study completion, an average of one month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Yan Qin, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking Union Medical College Hospital
name: Qi Miao, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70. doi: 10.1681/ASN.2004090740. Epub 2005 Sep 21.
citation: Hill P, Shukla D, Tran MG, Aragones J, Cook HT, Carmeliet P, Maxwell PH. Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 2008 Jan;19(1):39-46. doi: 10.1681/ASN.2006090998.
citation: Shu S, Wang Y, Zheng M, Liu Z, Cai J, Tang C, Dong Z. Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair. Cells. 2019 Feb 28;8(3):207. doi: 10.3390/cells8030207.
citation: Kapitsinou PP, Jaffe J, Michael M, Swan CE, Duffy KJ, Erickson-Miller CL, Haase VH. Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury. Am J Physiol Renal Physiol. 2012 May 1;302(9):F1172-9. doi: 10.1152/ajprenal.00667.2011. Epub 2012 Jan 18.
citation: Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, Tao Y, Liang X, Liu Z, Xing C, Chen J, Luo L, Zuo L, Liao Y, Liu BC, Leong R, Wang C, Liu C, Neff T, Szczech L, Yu KP. Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis. N Engl J Med. 2019 Sep 12;381(11):1001-1010. doi: 10.1056/NEJMoa1813599. Epub 2019 Jul 24.