Clinical trial NCT04356300: Exosome of Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection
Official title: Exosome of Mesenchymal Stem Cells for Multiple Organ Dysfuntion Syndrome After Surgical Repaire of Acute Type A Aortic Dissection: a Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Multiple Organ Failure
Lead sponsor: Fujian Medical University
Sponsor class: OTHER
First posted: 2020-04-22
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: totally 30 patient will be enrolled, and 15 patients will be given Exosomes of MSCs 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 Exosomes of MSC after onset of multiple organ dysfuntion syndrome after ascending aortic replacement combined with open placement of triple-branched stent graft for ATAAD.
Primary purpose: TREATMENT

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

Detailed description: Multiple organ dysfunction syndrome (MODS) are common debilitating complications after surgical repaired 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. There is increasing evidence that MSCs function in a paracrine manner. Exosomes have been reported to activate signaling pathways by binding to receptors. Compared with mesenchymal stem cells, exosomes are more stable and storable and no risk of aneuploidy. The possibility of immune rejection after allogeneic administration of exosomes is lower and can provide alternative treatment for a variety of diseases.

The trial contains two parts:

Part one (prevention scheme):to explore the safety and efficacy of exosome of MSC, the investigators will recruit patients who are diagnosed with ATAAD, and 15 participants will be administrated intravenously with exosome of MSC immediately after ascending aortic replacement combined with open placement of triple branched stent graft while other 15 not. Then the investigators will monitor participants' MODS related biochemical indexes, sequential organ failure assessment (SOFA) scores, comparing to those don't be treated with exosome of 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, the investigators will randomly use exosome of MSC to 15 of participants while other 15 not. Then the investigators will monitor participants' MODS related biochemical indexes, SOFA scores, comparing to those don't be treated with MSC. The dosage of the exosome of MSC was determined on the basis of the previous clinical studies, which is 180mg once a time and administrated intravenously.

Eligibility criteria: 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

Primary outcomes:
measure: survival after intervention
timeFrame: Up to 6 month
measure: sequential organ failure assessment score
timeFrame: Up to 6 months
measure: interleukin-6
timeFrame: Early 3 days
measure: The number of allergic reactions
timeFrame: Up to 6 months
measure: The number of people who get cancer
timeFrame: Up to 2 years
Secondary outcomes:
measure: the effects on kidney function
timeFrame: Up to 6 months
measure: the effects on liver function
timeFrame: Up to 6 months
measure: the effects on lung function
timeFrame: Up to 6 months
measure: the effects on coagulation function
timeFrame: Up to 6 months
measure: the effects on central nervous system
timeFrame: Up to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Union Hospital
name: Liang-wan Chen, M.D
role: PRINCIPAL_INVESTIGATOR
References: