Myocardial Reperfusion Injury
Conditions
Brief summary
The current study aims to evaluate different doses of PC-SOD injections for efficacy and safety in comparison to placebo, in order to provide a basis for future clinical trials in terms of experimental design and dose selection.
Detailed description
The study is a randomized, single-blind, multi-center, placebo-controlled trial to preliminarily evaluate the efficacy and safety of PC-SOD, and to provide a basis for dose selection in the next stage of study. For each participant, the trial will be divided into the screening/treatment (screening and treatment conducted during the first visit, 0 d) and safety follow-up (1 - 30 d) stages. The study will screen 120 eligible subjects. After successful screening, the subjects will be randomly assigned into four groups of equal size, including the 40 mg PC-SOD, 80 mg PC-SOD, 160 mg PC-SOD and placebo control groups. Subjects in each group will be administered the corresponding intervention, followed by PCI treatment. During the safety follow-up stage, the subjects will receive basic treatment based on Guidelines for Management of Patients with ST-segment elevation myocardial infarction. Treatments will include dual anti-platelet therapy, beta-blockers, ACEI/ARB (angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker), statins, anticoagulants, and so on. By comparing the efficacy and safety endpoints of patients in the experimental and placebo control groups, the study aims to preliminarily evaluate the efficacy and safety of different doses of PC-SOD in reducing myocardial reperfusion injury.
Interventions
DRUGPC-SOD
PC-SOD will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
DRUGplacebo
Placebo will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
Sponsors
Peking University First Hospital
Beijing Tide Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Since the appearance of PC-SOD preparations cannot be identical to that of placebo, and treatment groups have different administration doses, the study will be conducted in a single-blind manner, where only subjects (and families) are blinded and do not know whether they are treated by PC-SOD or placebo before unblinding. Interpretation of cardiac MRI and ECG will also be conducted in a blinding manner. Images of all subjects will be evaluated blindly by researchers not directly involved in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 - 75 years, male or female; 2. Meeting the diagnostic criteria of AMI (chest pain for over 10 - 20 min, which could not be relieved completely by oral nitroglycerin; ST elevation ≥ 2 mm in two or more adjacent leads in leads V1-V5 ); 3. Killip classes I or II; 4. Coronary angiography possible within 6 hours of onset; 5. Emergent coronary angiography showing occlusion in left anterior descending artery (TIMI grade 0 - 1); patients with this symptom could also be included despite inconformity to criterion 2); 6. Willingness to participate in the trial with ethical approval and informed consent provision.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The myocardial salvage index at 7 d after PCI | 7 days | The myocardial salvage index is defined as (area of myocardial edema - area of myocardial infarction)/area of myocardial edema. |
| The area of myocardial infarction at 7 d after PCI (detected by delayed-enhanced MRI [Magnetic Resonance Imaging] ) | 7 days | The area of myocardial infarction is defined as the percentage of left ventricular myocardium occupied by delayed enhancement. |
| Area of microvascular occlusion at 7 d after PCI | 7 days | Microvascular occlusion is defined as the area with no enhancement in the infarcted regions where delayed enhancement can be observed on MRI scans. |
| The area of infarction determined by the AUC (area under curve) for CK-MB (creatine kinase-muscle/brain) at 72h after PCI. | 72 hours | The area of infarction at 72h after surgery will be roughly estimated by calculating the AUC for CK-MB (before operation, and at 6, 12, 24, 48 and 72h after operation, respectively). |
| Cardiac function at 7 d after PCI | 7 days | Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume). |
| The TIMI (thrombolysis in myocardial infarction) grade of coronary blood flow after PCI. | within 24 hours | Coronary artery reperfusion will be assessed by the TIMI grading system, whose grades include: Grade 0: no contrast filling at the occlusion site and distal end; Grade 1: the contrast passes some of the occluded sites, but cannot fill the distal vessels; Grade 2: the contrast can fill the distal end of coronary artery completely, but the filling and clearing of contrast is slower than that of normal coronary artery; Grade 3: the contrast can fill the distal end rapidly and completely, and can be removed quickly. The TIMI flow grades will be determined by two physicians separately. In case of disagreement, a lead physician will help make the final call. |
| The corrected TIMI frame count (cTFC) after PCI. | within 24 hours | The left anterior descending (LAD) artery will be analyzed in a 30º right anterior oblique view with 30º cranial angulation. The left circumflex (LCX) will be analyzed in a 30º right anterior oblique view with 30º caudal angulation. The right coronary artery (RCA) will be analyzed in a 45º left anterior oblique view. |
| TIMI myocardial perfusion grade (TMPG) after PCI | within 24 hours | Grade 0: no contrast entering the myocardium; Grade 1: the contrast enters myocardium slowly, with myocardial staining not disappearing or lasting for more than 30 s in the targeted vessels; Grade 2: delayed entering and disappearing of contrast in the myocardium, exceeding 3 cardiac cycles; Grade 3: normal entering and disappearing of contrast in the myocardium, occurring within 3 cardiac cycles. |
| Percentage of ST-segment resolution on ECG (electrocardiogram) at 90 min after PCI | 90 minutes | ST-resolution is defined as more than 50% of resolution. |
| Number of cardiovascular events within 30 d after PCI | 30 days | Cardiovascular events included all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure. |
| SOD (Superoxide Dismutase) activity | 0 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after surgery | Change from Baseline SOD activity at 6h, 12h, 24h, 48h, 72h and 7 d after surgery. |
| Occurence of adverse events | During patient hospitalization, up to 30 days | Occurence of adverse events |
| Cardiac function at 30 d after PCI | 30 days | Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume). |
Countries
China
Contacts
Primary ContactHuo Yong, master
Outcome results
None listed