Clinical Trial of Mesenchymal Stem Cells in the Treatment of Severe Acute Kidney Injury

Study Overview
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Brief Summary
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Acute kidney injury(AKI) is a common, severe emergency case in clinics,especially severe AKI ,which is associated with higher morbidity and mortality. Effect of routine therapy is limited and mesenchymal stem cells (MSC)are considered a new therapy for treating severe acute kidney injury. Patients will be randomized to receive intravenous infusion of MSC, or placebo control. This trial is to investigate whether MSC can improve renal recovery and mortality of patients with AKI.

Official Title
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A Single-center, Randomized, Placebo-controlled, Patient-blinded Study of Mesenchymal Stem Cells Therapy in Subjects With Severe Acute Kidney Injury Receiving Routine Therapy

Conditions
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Acute Kidney Injury, Mesenchymal Stem Cells

Intervention / Treatment
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* Biological: Mesenchymal stem cells
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have severe AKI defined as more than two-fold increase serum creatinine level compared with baseline within 48 hours and/or urinary output consistently<0.5 ml/kg/h over 12 hours Age between 18 and 65 years Willing or having a legally acceptable representative to give a written informed consent Able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up Exclusion Criteria: AKI due to post-renal outflow obstruction,glomerulonephritis,lupus nephritis, antineutrophil cytoplasmic antibody (ANCA) related nephritis, antiglomerular basement membrane disease, cryoglobulinemia, thrombotic microangiopathy, and AKI caused by purpura nephritis Pregnant or lactating woman Allergic person Organ transplant or hematopoietic stem cell transplant Patients with malignant tumors or those with a history of cancer Life expectancy is less than 3 months Known end-stage liver disease Uncontrollable infection Patients younger than 65 years old ,whose estimated glomerular filtration rate (eGFR) were less than 60 Severe pulmonary dysfunction Severe cardiac dysfunction,left ventricular ejection fraction is less than 40%, or severe arrhythmia patients Hemodynamically unstable patients Organ failure affecting more than 2 non-renal organs Acute or chronic vasculitis of any cause History of chronic systemic infection of any cause The investigators believe that subjects may need to gradually increase the dose of vasopressor to achieve and / or maintain hemodynamic stability Systemic immunosuppressive therapy that has not been stabilized for greater than 4 months, or in the case of chronic corticosteroid therapy, a dose of >15 mg/day of prednisone or the equivalent within the past 30 days Platelet count <25,000/uL or other severe hematologic abnormalities, causing the subject to be at risk of death Patients need mechanical ventilation Participate in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells cohort<br> | Biological: Mesenchymal stem cells<br>* In experimental group, patients receive standard treatment and allogeneic human umbilical cord derived-mesenchymal stem cells (MSCs) is administered via intravenous infusion on day 0 and day 7<br>|
| Placebo Comparator: Saline cohort<br> | Other: Saline<br>* In placebo control group, patients receive standard treatment and saline is administered via intravenous infusion on day 0 and day 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the renal function between the two groups (MSC treatment group vs placebo control group) within 28 days after receiving MSC/ placebo treatment | Compare the creatinine concentration between the two groups (MSC treatment group vs placebo control group) at 28 days after receiving MSC/ placebo treatment. | within 28 days after receiving MSC/ placebo treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival within 28 days after receiving MSC/ placebo treatment | Compare the overall survival rate between the two groups (MSC treatment group vs placebo control group) at 28 days after receiving MSC/ placebo treatment. | 28 days | 
| Overall survival within 3 months after receiving MSC/ placebo treatment | Compare the overall survival rate between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/ placebo treatment. | 3 months | 
| Renal replacement therapy (RRT) dependent within 3 months after receiving MSC/ placebo treatment | Compare the rate of renal replacement therapy (RRT) dependence between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/ placebo treatment. | 3 months | 
| Complete renal recovery within 3 months after receiving MSC/ placebo treatment | Compare the rate of complete renal recovery between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. We considered complete recovery as alive, free of RRT, and the SCR decreased to no more than 1.5 times of the baseline level. | 3 months | 
| Partial renal recovery within 3 months after receiving MSC/ placebo treatment | Compare the rate of partial renal recovery between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. Partial recovery refers to survival, free of RRT, and the SCR 1.5 times higher than the baseline level of creatinine. | 3 months | 
| ICU and hospitalization duration of stay among all AKI patients within 3 months after receiving MSC/ placebo treatment | Compare the days in ICU and hospital between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. | 3 months | 
| Adverse events within 3 months after receiving MSC/ placebo treatment | Compare the rate of adverse events between the two groups (MSC treatment group vs placebo control group) at month 3 after receiving MSC/placebo treatment. | 3 months |