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

Primary Purpose

Coronary Artery Bypass

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Roxadustat
Placebo
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Coronary Artery Bypass focused on measuring acute kidney injury, coronary artery bypass, Roxadustat

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beijing Hospital
  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Roxadustat

placebo

Arm Description

Roxadustat

Placebo has the same appearance with the experimental drug (Roxadustat).

Outcomes

Primary Outcome Measures

acute kidney injury
elevation of serum creatinine ≥0.3mg/dl(26.5μmol/L)or ≥ 1.5 times baseline levels within 48 hours post surgery

Secondary Outcome Measures

classification of acute kidney injury
classification of of acute kidney injury based on AKIN criteria
renal function
creatinine, urea, Cystatin-C after surgery
new biomarkers of renal injury
serum and urine NGAL,urine TIMP2*IGFBP7
Cardiac Troponin Subunit I (cTnI)
peak plasma concentration of cTnI and area under curve (AUC) of cTnI
brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP)
plasma concentration of BNP
death
death during hospitalization
length of hospital stay and ICU stay
length of hospital stay and ICU stay
Blood infusion
amount of Red blood cells infusion after surgery
adverse events
adverse events and severe adverse events during hospitalization

Full Information

First Posted
August 7, 2021
Last Updated
April 18, 2022
Sponsor
Peking Union Medical College Hospital
Collaborators
Beijing Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05010460
Brief Title
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

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2021 (Actual)
Primary Completion Date
August 20, 2023 (Anticipated)
Study Completion Date
October 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Beijing Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Bypass
Keywords
acute kidney injury, coronary artery bypass, Roxadustat

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
318 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Roxadustat
Arm Type
Experimental
Arm Description
Roxadustat
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo has the same appearance with the experimental drug (Roxadustat).
Intervention Type
Drug
Intervention Name(s)
Roxadustat
Other Intervention Name(s)
Evrenzo
Intervention Description
orally 100mg every other day for 5-8 days prior to CABG
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
orally 100mg every other day for 5-8 days prior to CABG
Primary Outcome Measure Information:
Title
acute kidney injury
Description
elevation of serum creatinine ≥0.3mg/dl(26.5μmol/L)or ≥ 1.5 times baseline levels within 48 hours post surgery
Time Frame
0-48 hours after surgery
Secondary Outcome Measure Information:
Title
classification of acute kidney injury
Description
classification of of acute kidney injury based on AKIN criteria
Time Frame
0-3 days after surgery
Title
renal function
Description
creatinine, urea, Cystatin-C after surgery
Time Frame
0-3 days after surgery
Title
new biomarkers of renal injury
Description
serum and urine NGAL,urine TIMP2*IGFBP7
Time Frame
immediately after surgery and the first morning after surgery
Title
Cardiac Troponin Subunit I (cTnI)
Description
peak plasma concentration of cTnI and area under curve (AUC) of cTnI
Time Frame
0-3 days after surgery
Title
brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP)
Description
plasma concentration of BNP
Time Frame
0-3 days after surgery
Title
death
Description
death during hospitalization
Time Frame
through study completion, an average of one month
Title
length of hospital stay and ICU stay
Description
length of hospital stay and ICU stay
Time Frame
through study completion, an average of one month
Title
Blood infusion
Description
amount of Red blood cells infusion after surgery
Time Frame
0-3 days after surgery
Title
adverse events
Description
adverse events and severe adverse events during hospitalization
Time Frame
through study completion, an average of one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sanxi Ai, Doctor
Phone
+861069156874
Email
sanxiai@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Qin, Doctor
Phone
+861069156874
Email
qinyanbeijing@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yan Qin, Doctor
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Qi Miao, Doctor
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huaibin Wang, doctor
First Name & Middle Initial & Last Name & Degree
Huaibin Wang
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanxi Ai
Email
sanxiai@163.com
First Name & Middle Initial & Last Name & Degree
Yan Qin
Email
qinyanbeijing@126.com
First Name & Middle Initial & Last Name & Degree
Yan Qin
First Name & Middle Initial & Last Name & Degree
Qi Miao

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
qualified researchers can request access to anonymized individual patient-level data by contacting principle investigator of this study, but this does not mean all requests will be shared by the investigators.
IPD Sharing Time Frame
1 year after the end of this study
IPD Sharing Access Criteria
please contact the investigators through email in the time frame
Citations:
PubMed Identifier
16177006
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.
Results Reference
background
PubMed Identifier
18178798
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.
Results Reference
background
PubMed Identifier
30823476
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.
Results Reference
background
PubMed Identifier
22262480
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.
Results Reference
background
PubMed Identifier
31340089
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.
Results Reference
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Study of Roxadustat for Reducing the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting

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