Clinical trial NCT03007537
Conditions: Acute Kidney Injury Cardiac Disease Surgery
Keywords: Erythropoietin Cardiac Surgery Associated-acute Kidney Injury
Sponsor: Nanjing First Hospital, Nanjing Medical University
Start date: 2015-10-01; Completion date: 2018-12-28
Enrollment: 101 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To testify the prevention of Erythropoietin on cardiac surgery associated-acute kidney injury, and trying to provide evidence for protecting the renal function and improving the prognosis for patients after cardiac surgery.

Detailed description:
Patients meet the inclusion criteria and agree to sign an informed consent will be randomly assigned into the control group or erythropoietin group.Interventions will be applied 1 day(24hrs) before the cardiac surgery. Blood and Urine samples will be collected after the surgery. By using the criterion given by KDIGO2012 and testing the biomarkers for acute kidney injury, we hope to find out if there is an association between erythropoietin administration and the occurence of acute kidney injury.

Arms: arm 1: 0.9% sodium chloride 1ml, subcutaneous injection, once, applied 1day before cardiac surgery arm 2: 10000 IU erythropoietin, subcutaneous injection, once, applied 1day before cardiac surgery
Interventions: intervention 1: Erythropoietin intervention 2: 0.9% sodium chloride intervention 3: cardiac surgery
Intervention descriptions: intervention 1: 10000 IU erythropoietin, subcutaneous injection intervention 2: 0.9% sodium chloride 1ml, subcutaneous injection intervention 3: included valve, coronary artery bypass graft or surgery for congenital heart diseases

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Study Protocol and Statistical Analysis Plan 
 
Official Title of the study: Effects of erythropoietin on acute 
kidney injury in patients undergoing cardiac surgery 
ID: CSA-AKI2016 
NCT03007537 
Document Type: Study Protocol with Statistical Analysis Plan 
Document Date: August 4, 2020 
 
 
 


Acute renal injury (AKI) often occurs after cardiac surgery, while the incidence 
of cardiac surgery associated acute kidney injury (CSA- AKI) increases significantly 
in patients undergoing cardiopulmonary bypass during operation. The incidence of 
CSAAKI published in the current study was 8.9~39.0 %. Need of renal replacement 
therapy (RRT) was 1%~5% after operation, while the total mortality rate was about 
1.4%. Studies have shown that even minor postoperative AKI of elevated serum 
creatinine was significantly associated with higher mortality. Thus, the prevention of 
CSA-AKI is of great importance to improve the prognosis of patients. At present, the 
availability of effective drugs for CSA-AKI prevention drugs is still limited. 
Erythropoietin (EPO) is a kind of substance secreted by renal cortical 
tubulointerstitial cells and liver which is commonly used in the treatment of renal 
anemia. Studies have shown that EPO can prevent AKI due to the effect of potential 
anti-apoptotic and antioxidant. Previous documents also proved that EPO could 
improve renal function AKI models in rats. The safety of preoperative use has been 
preliminarily confirmed by some studies, but the conclusion of the effectiveness of 
renal protection still remains on controversial. The 2012 guidelines of AKI from 
Kidney Disease Improving Global Outcome (KDIGO) recommended randomized 
controlled studies conducted for EPO prevention of AKI. This study aimed to explore 
whether clinical use EPO can reduce the risk CSA-AKI in patients and improve the 
prognosis. 
1 Object and Methods 
1.1 Research subjects 
All patients received non-emergency cardiac surgery in Department of 
Cardiothoracic Surgery, Nanjing Hospital affiliated to Nanjing First Medical 
University from July 2016 to May 2017. 
Inclusion criteria: (1) 18 ~ 80 years old; (2) Preoperative hemoglobin < 130 g/L; 
(3) Surgical type: cardiopulmonary bypass, valvular or congenital heart disease 
surgery; (4) Signed the informed consent voluntarily. 
Exclusion criteria: (1) Suffering uncontrolled infection of other sites. (2) Refused 
to sign the informed consent; (3) Dialysis of end stage renal disease; (4) Had the 
history of acute myocardial infarction, acute cerebral infarction or pulmonary 
embolism in recent 3 months; (5) Chemotherapy for malignant tumors; (6) Suffering 
uncontrolled hypertension (systolic blood pressure >200mmHg, diastolic 
pressure >110 mmHg). (7) Allergic to erythropoietin. (8) Administration of 
erythropoietin in 2 weeks before the surgery. 
1.2 Research methodology 
This study was a single-center randomized controlled clinical trial (RCT). For 
patients recruited in the study, preoperative information and some laboratory test 
results were collected. Patients were randomly assigned 1:1 to the EPO group and the 
control group using the predetermined random allocation table. The EPO group 
received 10000 IU of single hypodermic injection 24 hours before the operation, and 
the control group received equal volume of normal saline. At the same time, all 
subjects were followed up in hospital 7 days after the operation. 


The test indicators included routine blood test, routine urine test and renal 
function test. Samples of blood and urine were collected at multiple time points before 
and after the surgery to detect early indicators of renal injury and inflammation. 
Including neutrophil Gelatinase associated lipocalin (NGAL), interleukin (IL-18), 
urinary kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), IL-6, etc. Other 
clinical index such as occurrence of postoperative AKI, length of hospital stay, 
intensive care unit stay time, renal replacement therapy (require renal replacement 
therapy), death, acute physiology and chronic health evaluation (APACHE Ⅱ) score, 
lung infections, etc. were collected.  
The diagnosis of AKI after cardiac surgery was based on the 2012 KDIGO AKI 
Guidelines. This study followed the Declaration of Helsinki and was approved by the 
Ethics Committee of Nanjing First Hospital (KY20160721-02). 
1.3 Statistical methods 
SPSS (V22.0, SPSS, Inc., Chicago, IL, USA) and Graphpad Prism 8.0 software 
were used for data analysis. Continuous data subject to normal distribution were 
expressed as mean ± standard deviation, and the independent sample T-test was used 
to compare the difference of the mean between the two groups. Repeated 
measurement design ANOVA was used to compare the differences between different 
groups at multiple time points. The categorical variables were presented as number 
(%) and compared by Pearson chi-square test.