Efficacy and Safety of Recombinant Human Thymosin β4(NL005) for Injection in Patients With Acute Myocardial Infarction: a Phase IIb Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Percentage change of myocardial infarction area
研究概览
简要总结
A multicenter randomized double-blind placebo parallel control design was used in this study. The 90 participants were randomly assigned to placebo, 0.5μg/kg dose group, and 1.0μg/kg dose group in a ratio of 1:1:1. After randomization, subjects received the trial drug or placebo intravenously within 12 hours and on days 2 to 7 after PCI. The patients were observed 90 days after PCI.
详细描述
Cardiovascular magnetic resonance imaging (CMR) was performed on day 5 and day 90 after PCI to evaluate myocardial infarction size, microvascular obstruction area, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). Physical examination, blood routine examination, and coagulation function examination were performed before the first dose, on the 7th, 30th, and 90th day after PCI. The examination before the first dose was conducted to accept the examination results from the current onset to the first dose.Electrocardiogram (ECG) was performed before the first dose, day 2, day 7, day 30, and day 90 after PCI, and the test results from the period after PCI to the first dose were received. Vital signs were examined before the first dose, day 1 to day 7, day 30, and day 90 after PCI, and the results of the examination from the first onset to the first dose were accepted during the examination before the first dose. Blood biochemical tests were performed before the first dose, from day 2 to day 4, day 7, day 30, and day 90 after PCI. The results of the examinations from the first onset to the first dose were accepted during the examination before the first dose. High-sensitivity troponin I(hs-cTnI) or troponin I(cTnI) and amino-terminal B-type natriuretic peptide precursor (NT-proBNP) or B-type natriuretic peptide (BNP) were tested before first administration and on days 2, 3, 4, and 7 after PCI. Examination results from the time after PCI to the time before initial administration; Creatine kinase isoenzyme (CK-MB) tests were performed before the first dose, 12 hours after the first dose, day 2 (if it coincided with 12 hours after the first dose, no repeat blood collection was required), day 3, and day 4. The test results from the period after PCI to the period before the first dose were accepted. Tumor markers were detected and immunogenic blood samples were collected before the first dose and on the 30th day after PCI. The tumor markers were examined before the first dose. Urine routine examination was performed before the first dose and on the 90th day after PCI. The examination before the first dose accepted the examination results from the onset of the disease to the first dose. Drug combinations, adverse events, and cardiovascular events were recorded during the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •The subjects or their guardians voluntarily participate in the experiment and sign the informed consent;
- •Age ≥18 years old and ≤75 years old, gender is not limited;
- •STEMI patients with proximal or/and middle occlusion of a single left anterior descending artery (TIMI grade 0-1) and PCI;
- •No coronary collateral (Rentrop grade 0);
- •meet one of the following conditions:
- •The total myocardial ischemia time before PCI was < 6 hours, and the TIMI grade after PCI was < 3
- •6 hours ≤ Total myocardial ischemia time before PCI ≤24 hours Note: Total myocardial ischemia time =PCI wire passage time - start time of chest pain
- •All subjects (male and female) must agree to use appropriate contraceptive methods (hormonal or barrier methods, abstinence) during study participation and up to 6 months of the last dosing, and women of childbearing age must test negative for pregnancy before dosing.
排除标准
- •Patients with a history of myocardial infarction who have received acute coronary thrombolysis, interventional therapy, or bypass surgery; A clear diagnosis of acute heart failure (Killip grade ≥III);
- •Severe arrhythmias that cannot be corrected;
- •Aortic dissection;
- •Severe liver and kidney dysfunction or severe consumption;
- •History of major surgery or hemorrhagic stroke within six months;
- •Previous history of malignant tumors;
- •Hypertensive patients with systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg after active antihypertensive treatment;
- •Clinically significant allergic reaction history, especially mannitol, drugs, protein preparations, biological products;
- •Patients who participated in other clinical studies within 3 months prior to screening;
- •Can not perform CMR examination;
- •Other conditions deemed unsuitable for inclusion by the investigators (for example, those whose coronary arteries other than the left anterior descending branch were judged by the investigators to require elective revascularization therapy at the same time or within 1 month).
研究组 & 干预措施
Middle Dose
12 hours after PCI: 0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
干预措施: NL005 Middle Dose (Drug)
High Dose
12 hours after PCI: 1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
干预措施: NL005 High Dose (Drug)
Placebo
Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage change of myocardial infarction area
时间窗: Day 5、Day 90
The percentage of myocardial infarction area was defined as the percentage of CMR delayed enhancement area in the entire left ventricular myocardium as measured by plane geometry of computer-assisted enhanced myocardium.Percentage change of myocardial infarction size =D5 percentage of myocardial infarction size -D90 percentage of myocardial infarction size
次要结局
- Myocardial mass (g)(Day 5、Day 90)
- Myocardial volume (ml)(Day 5、Day 90)
- The change of CK-MB before and after administration(Before the first dose, 12 hours after the first dose, day 2, day 3, day 4)
- The area under the CK-MB curve within 4 days(Before the first dose, 12 hours after the first dose, day 2, day 3, day 4)
- Changes of left ventricular end-systolic volume (LVESV)(Day 5、Day 90)
- Myocardial microvessel obstruction area change value(Day 5、Day 90)
- Changes of left ventricular ejection fraction (LVEF)(Day 5、Day 90)
- Changes of left ventricular end-diastolic volume (LVEDV)(Day 5、Day 90)