The Comparative Effectiveness of Alprostadil,Sodium Ferulate and Dopamine in Pediatric Acute Kidney Injury

Study Overview
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Brief Summary
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Acute kidney injury (AKI) is a pervasive clinical event in children.It has been independently associated with prolonged hospital stays, risk of in-hospital death and future progression to chronic kidney disease. Except for removal of nephrotoxic agents and optimization of supportive care,there are still no other effective therapeutic options recommended by recent guidelines. Renal ischemia is the main mechanism of AKI, the improving microcirculation therapy would be the effective management to improve the outcome of AKI in children. Dopamine is a vasodilating drug that in small doses improves renal circulation. Alprostadil have been used in chronic arterial occlusion and Sodium Ferulate in ischemic cerebral vascular disease,they have a similar therapeutic effect of anti-platelet aggregation and vasodilation. Recent research shows that alprostadil might be associated with a significant reduction in postcontrast Scr, blood urine nitrogen (BUN) and Cystatin C (CysC) level and decrease the incidence of contrast-induced nephropathy.The investigators speculate that Alprostadil,Sodium Ferulate and dopamine would be effective in treating AKI in children. This is a prospective, multicenter, randomized, double-blind, 52-week study. The purpose of this study is to evaluate the comparative effectiveness and safety of Alprostadil,Sodium Ferulate and dopamine in improving the outcome of AKI in children.

Detailed Description
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This study aims to explore the effective treatment of pediatric AKI and improve the outcome. It is a 52-week multicenter, randomized, double-blind,prospective study to evaluate comparative effectiveness and safety of alprostadil injection,sodium ferulate and dopamine injection. This study plans to recruit 8 to 10 centers, with 300 participants randomly divided into 3 groups and given respectively Alprostadil 0.2 0.3ug/kg.h,iv,1h/d,14d,Sodium Ferulate2 6mg/kg.d,iv,14d,Dopamine3 5ug/kg .min,iv,3h/d,14d.Time of outcome measurement is 1w,2w,4w,24w,52w. Primary Outcome Measures is The change of Serum creatinin from baseline, estimated glomerular filtration rate (eGFR) and urine volume in the participants after the use of the study drug.

Official Title
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A 52-week Multicenter, Randomized, Double-blind, Prospective Study to Evaluate Comparative Effectiveness and Safety of Alprostadil Injection,Sodium Ferulate and Dopamine Injection in Pediatric Acute Kidney Injury

Conditions
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Children AKI Patients

Intervention / Treatment
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* Drug: Alprostadil
* Drug: Sodium Ferulate
* Drug: Dopamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent signed and dated by participants and/or their guardians male or female, Asian. Aged from 1 to 18 years. Patients meet the AKI diagnosis criteria of 2012 Kidney Disease: Improving Global Outcome (SKDIGO) Guideline Exclusion Criteria: prerenal or postrenal failure Patients need renal replacement therapy Patients with hemorrhagic disorders Patients in shock Patients with multiple organ failure History of Alprostadil or Sodium Ferulate or dopamine sensitivity Patients with heart failure Patients with peptic ulcer Patients with glaucoma Patients with interstitial pneumonia

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprostadil<br>Alprostadil 0.2 0.3ug/kg.h,iv,1h/d,14d; Dopamine3～5 ug/kg·min,iv,3 h/d,14d | Drug: Alprostadil<br>* Alprostadil 0.2 0.3ug/kg.h,iv,1h/d,14d<br>Drug: Dopamine<br>* Dopamine3～5 ug/kg·min,iv,3 h/d,14d<br>|
| Active Comparator: Sodium Ferulate<br>Sodium Ferulate 2 6mg/kg.d,iv,14d; Dopamine3～5 ug/kg·min,iv,3 h/d,14d | Drug: Sodium Ferulate<br>* Sodium Ferulate 2 6mg/kg.d,iv,14d<br>Drug: Dopamine<br>* Dopamine3～5 ug/kg·min,iv,3 h/d,14d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinin | The change of Serum creatinin from baseline after the use of the study drug. | baseline, 52 weeks | 
| eGFR | The change of eGFR from baseline after the use of the study drug. eGFR (ml/min/1.73m2)=K×L/SCr. L: Height(cm), SCr: serum creatinin (umol/L),K:36.5 | baseline, 52 weeks | 
| Urine volume | The change of urine volume from baseline after the use of the study drug. | baseline, 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary markers：White Blood Cell (WBC) | Obtained through routine urine examination. | baseline, 52 weeks | 
| Urinary markers：Red Blood Cell (RBC) | Obtained through routine urine examination. | baseline, 52 weeks | 
| Urinary markers：Urine protein | Obtained through routine urine examination. | baseline, 52 weeks | 
| Serum urea | Obtained through renal function test. | baseline, 52 weeks | 
| Serum Cystatin | Obtained through renal function test. | baseline, 52 weeks | 
| Three dimensional(3D) color ultrasound Imaging | Size of kidneys,Blood flow of renal arteries. | baseline, 52 weeks | 
| Blood pressure |  | baseline, 52 weeks | 
| Duration of hospital stays |  | baseline, 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AKI, Child, Alprostadil, Sodium Ferulate, Dopamine