alprostadil liposomes for injection for lower extremity arteriosclerosis obliteran

Conditions: Peripheral Artery Disease

Summary: this is a randomized, positive-control, multicenter, multiple-dose, dose-escalation phase ii trial

a randomized, positive-control, multicenter, multiple-dose, dose-escalation phase ii trial. the trial was divided into 4 dose groups: the positive drug kaishi 10 μg group and the alprostadil liposome for injection 40μg, 80μg, 120μg group.

Eligibility criteria:
inclusion criteria: 1. 40 \<age ≤ 80 years ，regardless of gender; 2. agree to participate in this clinical trial and sign the informed consent voluntarily; 3. meet the diagnostic criteria of lower extremity arteriosclerosis obliteran (lower extremity aso) (according to the definition of the 2015 chinese lower extremity arteriosclerosis obliteran diagnosis and treatment guidelines), which are: age\> 40 years; have clinical manifestations of lower extremity arteriosclerosis obliteran ; weakness or disappearance of distal arterial pulsation in ischemic limbs; 4. ankle-brachial index (abi) \<0.9; 5. fontaine stage ii or iii. for subjects with fontaine stage ii, intermittent claudication distance is between 50m and 800m (fixed plate speed 3km / h, slope 12%); and at least 2 tests with difference of ≤25% (comparison based on the first measurement value, the second measurement is performed after the subject is fully rested the next day and after); 6. imaging examinations such as color doppler ultrasound, cta, mra, or dsa within 1 month before enrollment revealed lesions such as stenosis or occlusion of the corresponding lower limb arteries. exclusion criteria: 1. patients with pre-existing cardiac dysfunction, such as untreated heart failure, arrhythmia, coronary heart disease, mitral or aortic stenosis, or a history of myocardial infarction within the last 6 months; 2. combining a history of stroke or cerebral hemorrhage, the judgment of researchers will affect the safety evaluation of efficacy; 3. patients diagnosed or suspected of having pulmonary edema, pulmonary infiltration, or interstitial pneumonia through clinical or related examinations, or those with severe chronic obstructive ventilation disorder or respiratory insufficiency; 4. obesity (bmi≥40); 5. fontaine stage is iv, or patients with severe resting pain need to use strong analgesics or surgical amputation; 6. hepatic impairment (alt or ast ≥ 3 times uln) or primary liver disease; 7. renal dysfunction, scr\> 1.5 times the upper limit of normal value; 8. poorly controlled hypertension (systolic blood pressure ≥180 mmhg or diastolic blood pressure ≥110 mmhg); 9. diabetic patients with poor control (hba1c\> 9%); 10. patients with a history of interventional or bypass surgery or endovascular treatment in the past 3 months; or those who have stopped using prostaglandins for less than 5 half-life of the corresponding drugs; elderly within 5 half-life of the corresponding drug (such as naphthylamine, pentoxifylline, butrodil, cilostazol, etc.); 11. patients who have successfully received walking rehabilitation training in the past 6 months; 12. there are other diseases that significantly affect the walking distance, such as lower extremity joint disease, spinal disease, neuropathyt; 13. patients with inflammatory vascular diseases, such as multiple arteritis, peripheral edema, thrombo-occlusive vasculitis, etc .; 14. patients with total femoral or above, femoropopliteal artery occlusion, or above groin artery occlusion; 15. patients with active peptic ulcer or bleeding tendency; 16. glaucoma or hypertensive patients; 17. patients who have used powerful analgesics (such as morphine) in the nearly a month; 18. patients with mental illness or dementia; 19. patients with malignant tumors; 20. patients with previous allergies to similar products; 21. those who have participated in drug clinical trials in the past 3 months; 22. patients who are pregnant or nursing, or patients who are unable to perform effective contraception during the study period; 23. active hepatitis b virus infection (hbv surface antigen positive and (hbvdna quantification ≥1 × 103copies / ml), hepatitis c virus, syphilis antibody and hiv antibody positive; 24. other patients considered by investigators to be unsuitable for this trial.