Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection

Study Overview
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Brief Summary
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Multiple organ dysfunction syndrome (MODS) after surgical repaire for acute type A aortic dissection(ATAAD) is a life-threatening condition. In this study, patients who undergoing surgical repaire of ATAAD immdediately or presenting sever MODS after surgical repaire of acute type A aortic dissection will be treated with umbilical cord-derived mesenchymal stem cell.

Detailed Description
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Multiple organ dysfunction syndrome(MODS) are common debilitating complications after surgical repaire for ATAAD. MODS is one of the chief causes of post-operative death for acute type A aortic dissection(ATAAD) patients, and it was reported that MODS accounted for more than half of the death after surgery for ATAAD. Despite recent advance in surgical technique, mortality rate remains high in such critical care conditions. In animal models, studies have demonstrated the beneficial effects of MSCs with respect to ischemia-reperfusion injury of heart, lungs, kidney, brains and livers. Several pilot studies have provided evidence that MSC may be effective in treating critically ill patients with traumatic brain injury, acute renal failure, or acute respiratory distress syndrome. Therefore, in the present pilot study, the investigators hypothesized that timely initiation of mesenchymal stem cells(MSC) will positively influence survival and biochemical indexesof patients with MODS after ascending aortic replacement combined with open placement of triple-branched stent graft for ATAAD. The trial contain two parts: Part one(prenvention scheme): to explore the safety and efficacy of umbilical cord-derived MSC, we will recruit patients who are diagnosed with ATAAD, and 8 patients will be administrated intervenously with MSC immediately after ascending aortic replacement combined with open placement of triple-branched stent graft while other 8 not. Then we will monitor their MODS related biochemical indexes, sequential organ failure assessment(SOFA) scores, comparing to those don't be treated with MSC. Phase two(treatment scheme): for patients presenting severe MODS(SOFA score≥10) after ascending aortic replacement combined with open placement of triple-branched stent graft, we will randomly use MSC to 8 of patients while other 8 not. Then we will monitor their MODS related biochemical indexes, SOFA scores, comparing to those don't be treated with MSC. The dosage of the MSC was determined on the basis of the previous clinical studies, which is 1000000 cells per kilogram of body weight and administrated intervenously .

Official Title
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Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection: a Pilot Study

Conditions
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Multiple Organ Dysfunction Syndrome

Intervention / Treatment
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* Biological: MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Patients who are diagnosed with ATAAD and received emergency surgery with ascending aortic replacement combined with open placement of triple-branched stent graft elder than 60 years old Preoperative PaO2/FiO2 > 400mmHg, platelets ≥ 150*109/L, bilirubin < 20μmol/L, no hypotension (without vasoactive drugs), Glasgow Coma Score Scale = 15, creatine <110μmol/L Part 2: Patients who are diagnosed with ATAAD and received emergency surgery with ascending aortic replacement combined with open placement of triple-branched stent graft Patients who have failure of at least 2 organs Patients who meet the criteria as below: sequential organ failure assessment score (SOFA) ≥ 10 Exclusion Criteria: uncontrollable underlying disease life expectancy of less than 4 days history of long-term corticosteroid use during the past 6 months. The pre-operative computer tomography angiography(CTA) demonstrate the visceral arteries are involved pre-existing severe disease of any major organs

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Interventional Model Description: Part 1: totally 30 patient will be enrolled, and 15 patients will be given MSC immediately after ascending aortic replacement combined with open placement of triple-branched stent graft for ATAAD. Part 2: totally 30 patient will be enrolled, and 15 patients will be given MSC after onset of multiple organ dysfuntion syndrome after ascending aortic replacement combined with open placement of triple-branched stent graft for ATAAD.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cell<br>Patients in the MSC arm will be given MSC, i.v., 1000000 cells per kilogram of body weight. | Biological: MSC<br>* MSC at a dose of 1000000 cells per kilogram of body weight will be given intravenously once every 4 days for 4 times<br>|
| No Intervention: Control<br>Patients in the control arm will not be given MSC. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival after intervention | survival after intervention: comparing survival ratio in hospital(6 months post-intervention) between groups. | Up to 6 month | 
| adverse events | short term adverse events such as anaphylactic reaction, embolism; long term adverse events, such as oncogenicity | Up to 2 years | 
| sequential organ failure assessment score(SOFA) | Compare the change of sequential organ failure assessment score(SOFA) between groups. | Up to 6 months | 
| interleukin-6 | Compare the change of interleukin( IL)-6 between groups. | Early 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effects on kidney function | the therapeutic effects in the improvement of kidney function, as indicated by Scr level. | Up to 6 months | 
| the effects on liver function | the therapeutic effects in the improvement of liver function, as indicated by bilirubin levels. | Up to 6 months | 
| the effects on lung function | the therapeutic effects in the improvement of lung function, as indicated by oxygenation index. | Up to 6 months | 
| the effects on coagulation function | the therapeutic effects in the improvement of coagulation function, as indicated by blood platelet count. | Up to 6 months | 
| the effects on central nervous system | the therapeutic effects in the improvement of coagulation function, as indicated by Glosgow coma score | Up to 6 months |