Anfibatide Phase Ib-IIa Clinical Trial

Study Overview
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Brief Summary
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Investigate the safety and efficacy of Anfibatide in non-ST segment myocardial infarction patients

Detailed Description
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This study is a phase Ib-IIa exploratory study to observe the safety of Antiplatelet Thrombolysin for Injection for the treatment of non-ST segment myocardial infarction (NSTEMI) patients and preliminarily evaluate the efficacy of different doses, providing the theoretical basis of the phase II and III clinical study protocol. To investigate the pharmacokinetics of different doses.

Official Title
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A Multi-center, Randomized, Double-blind, Multi-dose Group, Parallel Group and Placebo Controlled Phase Ib-IIa Clinical Study to Evaluate the Safety and Efficacy of Antiplatelet Thrombolysin for Injection for the Treatment of Patients With Non-ST Segment Elevation Myocardial Infarction (NSTEMI).

Conditions
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Non-ST Segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Anfibatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years; Laboratory tests show increase of the markers of myocardial damage (CK-MB,CTnI), or reduction after increase, with at least one values exceeding the 99th percentile of the upper limit of the reference value; Ischemia symptoms (ischemic chest pain lasts for over 15 minutes, little release after taking nitroglycerin sublingually) or a new myocardial ischemia on electrocardiogram(ECG), i.e. a new ST-T variation (a new or transient depression of ST segment by over 0.1mV, or T-wave inversion≥0.2mV); Patients receive PCI after coronary angiography; Patients, or their family or guardian give signed informed consent forms. Exclusion Criteria: Patients with severe unstable hemodynamics who should receive urgent PCI; Patients with untreated hypertension (SBP>180 mmHg or DBP >110mmHg) and hypotension shock (SBP<90mmHg/80mmHg for over 30min); Investigator considers patients need to use GPIIb/IIIa receptor antagonists during the study period; After coronary angiography, the number of stenosed vessels >2；lesions in left main branch, severe calcification and artery graft lesions; Patients with heart function in decompensatory phase (Killip grade 3-4) or cardiac shock; Patients with malignant arrhythmia, e.g. the third-degree atrioventricular block, ventricular tachycardia or fibrillation ventricular; Patients with severe hepatic or renal dysfunction, with serum aspartate transaminase(AST) and alanine transaminase (ALT) exceeding 1.5 times the upper limit of reference values, creatinine clearance <30ml/min or serum creatinine ≥200μmol/L or 2.5mg/dl; Patients who have received PCI in the past six months; Patients who have received coronary artery bypass grafting (CABG) previously; Patients who have received invasive operation in the past 3 months; Patients who have suffered from ischemic stroke or transient ischemic attack (TIA) in the past 6 months, or patients with past history of hemorrhagic stroke; Patients who need a long-term treatment of oral anticoagulants (such as warfarin); Patients with active peptic ulcer, or other diseases of hemorrhagic tendency; Patients with disease of coagulation disorder; Hematology test shows platelet count <100,000mm3,or hemoglobin<100g/L; Women in pregnant or lactation period, or women of child-bearing age do not take efficient contraception measures; Patients with an allergic constitution; Patients who is participating in other clinical trials; Patients who do not give a signed informed consent forms; Patients who are not suitable to enroll in the trial according to the investigator's judgement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anfibatide<br>Bolus injection will be finished in 5 minutes immediately when the guidewire passes through the first stenosed vessel; bolus injection of different doses+0.002IU/kg/h intravenous infusion for 48h | Drug: Anfibatide<br>* Snake venom<br>|
| Placebo Comparator: Placebo<br>Bolus injection will be finished in 5 minutes immediately when the guidewire passes through the first stenosed vessel; bolus injection of different doses+0.002IU/kg/h intravenous infusion for 48h | Drug: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregation | The inhibition of ristocetin-induced platelet aggregation as measured by whole blood impedance aggregometr in vitro. | up to 48 hours | 
| Bleeding events | Bleeding events classified according to the Bleeding Academic Research Consortium (BARC) . | Day 0 to day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | all-cause mortality, relapse of nonfatal myocardial infarction, nonfatal stroke, second target vascular reconstructio. | 30 days after treatment | 
| Safety Endpoints | Degree of thrombocytopenia; Moderate (<100,000 platelets/mm3); Severe (<50,000 platelets/mm3); Extremely severe (<20,000 platelets/mm3) | Day 0 to day 30 | 
| Thrombosis formation | Thrombosis formation after stent implantation: | 48 hours after infusion during operation | 
| Thrombolysis in myocardial infraction (TIMI) | The proportion of TIMI from grade 0 to 3 Pre -and post-PCI was evaluated. | day 0 | 
| Corrected TIMI frame count（CTFC） | The values of CTFC were evaluated and compared between groups. | day 0 | 
| TIMI myocardial perfusion grade （TMBG） | The proportion of TMPG from grade 0 to 3 Pre -and post-PCI was evaluated. | day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-platelet;, safety;, efficacy