Clinical Study on Ischemia-Reperfusion Injury Using Intravenous Administration of MSC in Patients With Myocardial Infarction Intended to Improve MVO and Prognosis After Surgery
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 90
- 主要终点
- IS
研究概览
简要总结
The investigators scheduled to assess the value of intravenous injection of WJ-MSC in patients with ST-segment elevation myocardial infarction (STEMI).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 75;
- •First performance of anterior acute ST-segment elevation myocardial infarction (STEMI), Killip grade 2 or below on admission;
- •Completing emergency percutaneous coronary intervention within 12h, with TIMI flow grade 0 or 1 (before stent implantation) and 3 (after stent implantation);
- •LVEF in echocardiography is 45% or below primary PCI.
排除标准
- •Medical history of Q wave myocardial infarction, significant valve disease, pericarditis, pericardial tamponade, myocardiopathy, chronic heart failure or cardio embolism;
- •Non ST-segment elevation myocardial infarction;
- •Chronic occlusion in LCX or RCA besides LAD;
- •Diagnosed with severe coronary artery disease but not yet causing a loss of heart function;
- •Hemodynamic disorders, shock or respiratory failure on admission;
- •Atrial fibrillation with warfarin treatment only or at high risk of bleeding;
- •Constant tachycardia, malignant arrhythmia, complete atrioventricular block, new-onset complete left bundle branch block (LBBB) or pacemaker implantation;
- •Mechanical complications of acute myocardial infarction (interventricular septal defect, rupture of papillary muscle, etc.) or huge left ventricular aneurysm could only be corrected through surgical procedures;
- •Chronic pulmonary heart disease (COPD, bronchial asthma, chronic bronchitis, emphysema or pulmonary heart disease), autoimmune disease or patients on immunosuppressive therapy;
- •Acute infective disease;
- •Hepatitis B/C virus or HIV;
- •Blood system diseases (thrombocytopenia, severe anemia, leukemia, etc.);
- •Severe renal insufficiency, with creatinine clearance (CCr) <33 ml/min or serum creatinine >133 μmol/L;
- •Obvious abnormalities in liver function (ALT and AST 3 times higher than the upper limit of normal value);
- •Medical history of cerebral hemorrhage;
- •Medical history of the malignant tumor;
- •Cognitive impairment, dementia or severe mental illness (SMI);
- •Substantial disability negatively influenced regular follow-up research;
- •Systematic diseases not been effectively controlled or life expectancy < 1 year;
- •Pregnant or lactating women;
- •Not suitable for MRI examination, or could not stick to treatment plans;
- •Could not or not willing to give written informed consent.
- •Exit Criteria:
- •Intolerable infaust events or changed treatment strategy leading to serious violations of trial conduct;
- •Requiring to exit the clinical trial;
- •Research scheme violations, severely disrupted safety and effectiveness of the trail;
- •Lost to follow-up cases;
- •Conceiving children or want to do that during the treatment period;
- •Candidates not fit to carry on the trial.
研究组 & 干预措施
WJ-MSC cells implantation group
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".
干预措施: WJ-MSC cells implantation (Biological)
WJ-MSC cells implantation group
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".
干预措施: Conventional drug therapy (Drug)
CTSTMD PBS without WJ-MSC group
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".
干预措施: CTSTMD PBS without WJ-MSC (Drug)
CTSTMD PBS without WJ-MSC group
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".
干预措施: Conventional drug therapy (Drug)
结局指标
主要结局
IS
时间窗: at Month 3 after treatment.
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.
次要结局
- MVO and Hemorrhage(at Day 4 to Day 7 after PCI.)
- CMR Markers of Myocardial and Microvascular Damage(at Month 3 after PCI.)
- Serum BNP(at Hour 7, Month 1, Month 6 and Year 1 after PCI.)
- MACCE(within 1 year after PCI.)
- CK-MB and Troponin(at baseline and at Hour 6, Hour 12, Hour 24 and Hour 48 after PCI.)
- Echocardiographic Changes(at Hour 6, Week 1, Month 1, Month 6 and Year 1 after PCI.)
- 6-min Walk Test(at Hour 6, Week1, Month 1, Month 6 and Year 1 after PCI.)
- MLHFQ Scale(at Week1, Month 1, Month 6 and Year 1 after PCI.)
研究者
Biao Xu
Professor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School