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

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Organ Dysfunction Syndrome
• Intervention / Treatment: Biological: MSC

Detailed Description

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 .

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Department of Cardiovascular Surgery
      • Contact: E Lin, M.D; Phone Number: 86 13365912195; Email: 1470054258@qq.com
      • Contact: Liang-Wan Chen, M.D, Ph.D; Phone Number: 86 13358255333; Email: daixiaofu719@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fujian Medical University
• Investigators: Principal Investigator: Liangwan Chen, M.D, Union Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: June 10, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: June 16, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Shock; Aneurysm; Syndrome; Aneurysm, Dissecting; Multiple Organ Failure
• Other Study ID Numbers: 2018005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No