Therapeutic Angiogenesis for Peripheral Artery Occlusive Disease Using Hyaluronan Combined With Autologous Bone Marrow Cell Therapy -- Phase I/II Safety and Efficacy Study
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 4
- 主要终点
- Ankle Brachial Index (ABI)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of hyaluronan combined with autologous bone marrow mononuclear cells for the treatment of critical PAOD patients.
详细描述
This is a multicenter, non-blinded and randomized study to evaluate the safety and efficacy of hyaluronan (HA) combined with autologous bone marrow mononuclear cells (BMMNC) therapy for critical peripheral arterial occlusive disease (PAOD) patients.
A total of 30 subjects will be recruited into the study. The subjects will be randomized into 3 different arms. During the Phase I study, 9 subjects recruited while another 21 additional subjects will be recruited in Phase II after the review of DSMB and consultation of Taiwan FDA on the results of the Phase I study.
Each subject will be administered 5~10 injections of RV-P1501, the number of injections depends on the size of the subject's ischemic leg. Each subject will receive treatment once. Subjects will be assigned to the treatments in random order. Evaluations including ABI, PWT/PFWT, clinical status, EF, CTA, biochemistry and hematology checked during the inclusion and exclusion evaluation, and will be taken at baseline, 1 week, 2 weeks, 4 weeks, 12 weeks, and 24 weeks after the treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient age ≥ 20
- •Patients with severe PAOD and diagnosed with Rutherford category 3, 4, or 5
- •Contraindication to angioplasty or bypass surgery, or post-angioplasty or bypass surgery for once but with limited or no effect.
- •Patient without hypertension or hypertensive patient with adequate-controlled blood pressure.
- •With signed informed consent
排除标准
- •Patient undergone any organ transplantation
- •Inability to undergo bone marrow aspiration
- •Pregnant woman
- •Life expectancy < 1 year
- •Cognitive impairment
- •Active malignancy in 5 years prior to treatment
- •Bleeding diathesis or pulmonary embolism
- •Patient with active major cardiovascular diseases such as unstable angina, arrhythmia, heart failure, impaired cardiac function (ejection fraction < 45%), or stroke
- •Estimated Glomerular Filtration Rate (eGFR) < 30
- •Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values higher than 80 U/L
- •Patient with severe diabetes mellitus (HbA1C > 8%)
- •Patient with alcohol addiction
- •Patient with drug abuse
- •Patient with infections or skin disease on the ischemic leg.
- •Allergic to HA
- •Patient whose blockage region only occurred in the femoral artery or at foot.
结局指标
主要结局
Ankle Brachial Index (ABI)
时间窗: Day 0, Week 4, Week 12, Week 24
The percentage change of ABI from 3 follow-ups with the baseline.
次要结局
- Hematology(Week 12, Week 24)
- Clinical status (Rutherford category)(Day 0, Week 1, Week 2, Week 4, Week 12, Week 24)
- Level of pain at rest(Day 0, Week 1, Week 2, Week 4, Week 12, Week 24)
- Ulcer size in cm2(Day 0, Week 1, Week 2, Week 4, Week 12, Week 24)
- PWT/PFWT in seconds(Day 0, Week 4, Week 12, Week 24)
- Amputation free(Week 1, Week 2, Week 4, Week 12, Week 24)
- Ulcer category(Day 0, Week 1, Week 2, Week 4, Week 12, Week 24)
- Ejection fraction(Week 12, Week 24)
- CT angiography(Week 12, Week 24)
- Biochemistry(Week 12, Week 24)