Clinical trial NCT03995732: Efficacy and Safety Evaluation of PC-SOD for Injection in Reducing Myocardial Reperfusion Injury
Official title: Efficacy and Safety Evaluation of Phosphatidyl Choline Cu/Zn Superoxide Dismutase (PC-SOD) for Injection in Reducing Myocardial Reperfusion Injury: a Multicenter, Randomized, Single-blind, Placebo-controlled Dose-finding Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myocardial Reperfusion Injury
Lead sponsor: Beijing Tide Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Peking University First Hospital
First posted: 2019-06-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria

1. Previous history of myocardial infarction;
2. History of myocardial revascularization before screening;
3. Thrombolytic treatment after onset;
4. Cardiogenic shock;
5. Cardiopulmonary resuscitation between onset and screening;
6. Atrial fibrillation, atrioventricular block (degree I, II or III), and other severe arrhythmias that cannot be corrected and affect hemodynamics;
7. Suspected of aortic dissection;
8. Diabetes with long-term insulin use, or definite macrovascular or small vascular lesions (stroke, diabetic nephropathy, retinopathy, diabetic foot, and etc.);
9. History of major surgeries within 6 months;
10. History of stroke within 6 months;
11. History of immune disorders within 6 months (such as cancer, lymphoma, HIV or hepatitis), or use of immunosuppressive agents at doses that can cause immunosuppression within 10 days;
12. Clinically significant diseases of the respiratory, digestive, blood, immune, endocrine, nervous or urinary systems (renal insufficiency in particular), and diseases that might cause serious risk to patients based on the judgement of researchers;
13. Allergy to two or more drugs and/or foods, or known allergy to sucrose;
14. Any contraindications for cardiac MRI, such as implantation of metal objects (pacemakers and/or implantable defibrillators; insulin pumps, or any other electronic devices; cerebral clips, aneurysm clips, and etc.), and other contraindications (such as claustrophobia);
15. Pregnancy or lactation in women;
16. Participation in other clinical trials within 3 months;
17. Situations considered unsuitable for enrollment (such as disease condition or patient compliance).

Exclusion criteria for angiography

1. Occlusion of left main artery;
2. Apart from the left anterior descending branch, other blood vessels requiring revascularization in the same period or within a month.

Primary outcomes:
measure: The myocardial salvage index at 7 d after PCI
timeFrame: 7 days
measure: The area of myocardial infarction at 7 d after PCI (detected by delayed-enhanced MRI [Magnetic Resonance Imaging] )
timeFrame: 7 days
measure: Area of microvascular occlusion at 7 d after PCI
timeFrame: 7 days
measure: The area of infarction determined by the AUC (area under curve) for CK-MB (creatine kinase-muscle/brain) at 72h after PCI.
timeFrame: 72 hours
measure: Cardiac function at 7 d after PCI
timeFrame: 7 days
measure: The TIMI (thrombolysis in myocardial infarction) grade of coronary blood flow after PCI.
timeFrame: within 24 hours
measure: The corrected TIMI frame count (cTFC) after PCI.
timeFrame: within 24 hours
measure: TIMI myocardial perfusion grade (TMPG) after PCI
timeFrame: within 24 hours
measure: Percentage of ST-segment resolution on ECG (electrocardiogram) at 90 min after PCI
timeFrame: 90 minutes
measure: Number of cardiovascular events within 30 d after PCI
timeFrame: 30 days
measure: SOD (Superoxide Dismutase) activity
timeFrame: 0 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after surgery
measure: Occurence of adverse events
timeFrame: During patient hospitalization, up to 30 days
measure: Cardiac function at 30 d after PCI
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Asia Heart Hospital
state: Hubei
city: Shanghai
country: China
facility: Zhongshan Hospital
state: Shanghai
Study officials:
References:
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