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

Coronary Artery Bypass Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05010460
• Other study ID #: ROXAKI
• Status: Recruiting
• Phase: Phase 2
• Start date: September 30, 2021
• Est. completion date: October 30, 2023

Study information

• Verified date: August 2021
• Source: Peking Union Medical College Hospital
• Contact: Sanxi Ai, Doctor
• Phone: +861069156874
• Email: sanxiai[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 318
• Est. completion date: October 30, 2023
• Est. primary completion date: August 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Coronary Artery Bypass

Intervention

Drug:
• Roxadustat
orally 100mg every other day for 5-8 days prior to CABG
• Placebo
orally 100mg every other day for 5-8 days prior to CABG

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Beijing Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View 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. Epub 2005 Sep 21. — View 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. — View 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. — View 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). pii: E207. doi: 10.3390/cells8030207. Review. — View Citation

Outcome

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