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The investigators scheduled to assess the value of intravenous injection of WJ-MSC in patients with ST-segment elevation myocardial infarction (STEMI).
Ischemia/reperfusion injury in myocardial infarction can induce mass release of oxygen free radicals, trigger inflammatory reaction, and ultimately lead to myocardial remodeling and irreversible cardiac function decline. Microvascular obstruction (MVO) and haemorrhage are common pathological alternations in myocardium post primary PCI, which provide strong prognostic information for STEMI patients. Till now, there is no treatment to be used in clinical practice to reduce myocardium MVO and haemorrhage. With the deep research on stem cells, it is found that the benefits of MSC transplants for myocardium infarction may be achieved by its paracrine effect. Meanwhile, the immunoregulatory effect of MSC has been widely reported in multiply immune disease. Therefore, the applicant proposed the hypothesis that MSC can play an effective role in reducing oxidative stress and inflammatory response, inhibiting microvascular obstruction and haemorrhage. Intravenous injection of MSC will be used in patients with STEMI within 12 hours post primary PCI. The primary endpoint and safety endpoint are recorded in the one year follow up to assess the clinical outcome of intravenous MSC treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WJ-MSC cells implantation group | Experimental | MSC cells (allogeneic transplantation from WJ-MSC primary cells); the frequency: for one time within12h after emergency coronary artery revascularization; dose levels: 1X10^8; method of administration: intravenous injection. Other kinds of treatment are in accordance with the treatment guidelines for MI patients, listed in the column "Conventional drug therapy". |
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| CTSTMD PBS without WJ-MSC group | Placebo Comparator | Saline only was injected in the control group. The frequency: for one time 2-12h after emergency coronary artery revascularization. Dose levels: the same dosage given to MSC group. Method of administration: intravenous injection. Other kinds of treatment are in accordance with the treatment guidelines for MI patients, listed in the column "Conventional drug therapy". |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WJ-MSC cells implantation | Biological | Laboratory of Stem Cell of Drum Tower Hospital, Nanjing University Medical School, is able to provide types of Good Manufacture Practice (GMP) level stem cells and stem cell-based medicinal products. Clinical-grade WJ-MSC primary cells are cultured to 4~ 8 passages, and the surface markers (CD90+, CD105+, CD45-, CD31-, CD117-) are identified by flow cytometry. WJ-MSC cells are trypsinized and resuspended in the wash buffer of CTSTMD PBS (+Ca2+, +Mg2+). Within 2 hours after enzyme digestion, WJ-MSC cells are shipped to coronary care unit (CCU) and injected into the body. |
| Measure | Description | Time Frame |
|---|---|---|
| IS | The primary endpoint is based on patients' myocardial infarction size (IS) as a result of CMR examination. The detection is recorded in the follow up at Month 3. | at Month 3 after treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| MACCE | Follow up main adverse cardiovascular and cerebrovascular events (MACCE) such as death, myocardial infarction, stroke and heart failure within 1 year after treatment. | within 1 year after PCI. |
| MVO and Hemorrhage |
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Inclusion Criteria:
Exclusion Criteria:
Exit Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| ZILUN WEI, PGT | Contact | 86-18066045583 | ljdwdth@outlook.com | |
| JUN XIE, Ph.D. | Contact | 86-13913859989 | darcy_pann@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| BIAO XU, Ph.D. | Drum Tower Hospital, Nanjing University Medical School | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28728654 | Background | Ahn JM, Park DW, Lee CW, Chang M, Cavalcante R, Sotomi Y, Onuma Y, Tenekecioglu E, Han M, Lee PH, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Comparison of Stenting Versus Bypass Surgery According to the Completeness of Revascularization in Severe Coronary Artery Disease: Patient-Level Pooled Analysis of the SYNTAX, PRECOMBAT, and BEST Trials. JACC Cardiovasc Interv. 2017 Jul 24;10(14):1415-1424. doi: 10.1016/j.jcin.2017.04.037. | |
| 28823746 |
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We have not decided to make it open.
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| CTSTMD PBS without WJ-MSC | Drug | For Case-control study only. |
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| Conventional drug therapy | Drug | All patients undergo guideline-recommended treatment for STEMI, including aspirin (loading dose of 300mg before maintenance dose of 100 mg/d), clopidogrel (loading dose of 300mg before maintenance dose of 75 mg/d) or Ticagrelor (loading dose of 300mg before maintenance dose of 90 mg/d), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), β-receptor blockers, statins and nitrate esters. |
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Patients underwent cardiac magnetic resonance imaging (CMR) at Day 4 to Day 7 after presentation with STEMI on a 3.0-T scanner.The change in Microvascular obstruction (MVO) and intramyocardial hemorrhage would be followed up. MVO was defined (and quantified) as hypoenhancement within infarcted myocardium, as determined from LGE images, and was included in the total infarct size. Myocardial oedema was quantified using semi-automatic thresholding, defining AAR as enhancement within myocardium of signal intensity > 2 standard deviations (SDs) above that of a region of interest contoured in remote myocardium. Hypoenhanced areas within the AAR were regarded as intramyocardial haemorrhage (IMH). The MSI was calculated as 100 × [(AAR - infarct size)/AAR]. Infarct size, MVO, AAR and IMH were expressed as %LVM and LV volumes were indexed to body surface area.
| at Day 4 to Day 7 after PCI. |
| CMR Markers of Myocardial and Microvascular Damage | CMR markers of myocardial and microvascular damage (myocardial salvage, left ventricular end diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), microvascular obstruction (MVO), intramyocardial hemorrhage) would be followed up at Month 3 after treatment. | at Month 3 after PCI. |
| CK-MB and Troponin | A sensitive troponin T assay for the early diagnosis and risk stratification of myocardial infarction would be evaluated. Blood samples were drawn at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PPCI for cardiac enzyme [creatine kinase MB isoenzyme (CK-MB) and troponin] estimation | at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PCI. |
| Echocardiographic Changes | Changes in echocardiography would be tested at Hour 6, Week 1, Month 1, Month 6 and Year 1 after treatment. | at Hour 6, Week 1, Month 1, Month 6 and Year 1 after PCI. |
| 6-min Walk Test | Changes in 6-min walk test would be tested at Hour 6, Week1, Month 1, Month 6 and Year 1 after treatment. | at Hour 6, Week1, Month 1, Month 6 and Year 1 after PCI. |
| Serum BNP | Changes in patients' serum BNP level would be tested at Hour 7, Month 1, Month 6 and Year 1 after treatment. | at Hour 7, Month 1, Month 6 and Year 1 after PCI. |
| MLHFQ Scale | Patients would be required to fill out the quality of life (QQL) scale Minnesota Living with Heart Failure Questionnaire (MLHFQ) at Week1, Month 1, Month 6 and Year 1 after treatment. | at Week1, Month 1, Month 6 and Year 1 after PCI. |
| Background |
| Symons R, Pontone G, Schwitter J, Francone M, Iglesias JF, Barison A, Zalewski J, de Luca L, Degrauwe S, Claus P, Guglielmo M, Nessler J, Carbone I, Ferro G, Durak M, Magistrelli P, Lo Presti A, Aquaro GD, Eeckhout E, Roguelov C, Andreini D, Vogt P, Guaricci AI, Mushtaq S, Lorenzoni V, Muller O, Desmet W, Agati L, Janssens S, Bogaert J, Masci PG. Long-Term Incremental Prognostic Value of Cardiovascular Magnetic Resonance After ST-Segment Elevation Myocardial Infarction: A Study of the Collaborative Registry on CMR in STEMI. JACC Cardiovasc Imaging. 2018 Jun;11(6):813-825. doi: 10.1016/j.jcmg.2017.05.023. Epub 2017 Aug 16. |
| 24135835 | Background | Cuculi F, Dall'Armellina E, Manlhiot C, De Caterina AR, Colyer S, Ferreira V, Morovat A, Prendergast BD, Forfar JC, Alp NJ, Choudhury RP, Neubauer S, Channon KM, Banning AP, Kharbanda RK. Early change in invasive measures of microvascular function can predict myocardial recovery following PCI for ST-elevation myocardial infarction. Eur Heart J. 2014 Aug 1;35(29):1971-80. doi: 10.1093/eurheartj/eht434. Epub 2013 Oct 17. |
| 23594591 | Background | Robbers LF, Eerenberg ES, Teunissen PF, Jansen MF, Hollander MR, Horrevoets AJ, Knaapen P, Nijveldt R, Heymans MW, Levi MM, van Rossum AC, Niessen HW, Marcu CB, Beek AM, van Royen N. Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage. Eur Heart J. 2013 Aug;34(30):2346-53. doi: 10.1093/eurheartj/eht100. Epub 2013 Apr 17. |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
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| ID | Term |
|---|---|
| D003226 | Congresses as Topic |
| ID | Term |
|---|---|
| D009938 | Organizations |
| D004472 | Health Care Economics and Organizations |
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