Laurora G, Corsi M, Bucci M, Cesarone M R, Belcaro G, Dugall M
Angiology and Vasc. Surgery, Clinical Trials Unit, Pierangeli Clinic, Pescara.
Minerva Cardioangiol. 1998 Oct;46(10 Suppl 1):21-9.
The efficacy, safety and cost of prostaglandin E1 (PGE1 alpha-ciclodestrina) in the treatment of severe intermittent claudication was studied comparing a long term treatment protocol (LTP) with a short term treatment protocol (STP) in a randomised, 20-week study.
The study has selected 120 patients (109 were included and 99 completed the study). The average total walking distance at inclusion was 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP phase 2 was the main treatment phase. The treatment was performed with 2-hour infusions (60 micrograms PGE1 alpha-ciclodestrina, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 alpha-ciclodestrina was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in two days with a 2-hour infusion (1st day: morning 20 micrograms, afternoon 40 micrograms; 2nd day 60 micrograms, morning and afternoon). The reduced dosage was used only at the first cycle to evaluate reduced tolerability or side effects. Full dosage (60 micrograms b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, 12 (phase 3). The observation period was between weeks 12 and 20 (phase 4). For both protocols a treadmill test was performed at inclusion, at the beginning of each phase and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors plan was used in both groups.
Intention-to-treat analysis indicated an increase in walking distance which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% in STP vs 107.3% in LTP) and at 20 weeks (351% in STP vs 242% in LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild, adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. The average cost of LTP was approximately 6.588 ECU; for STP the average costs was approximately 1881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; P < 0.02). For an average 100% increase in walking distance LTP cost was 1937 ECU vs 550 ECU with STP (P < 0.02). The cost of PGE1 alpha-ciclodestrina (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP).
In summary between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 alpha-ciclodestrina treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation and may be used in a larger number of non-specialised units available to follow the protocol.
在一项为期20周的随机研究中，通过比较长期治疗方案（LTP）和短期治疗方案（STP），研究了前列腺素E1（前列地尔α-环糊精）治疗重度间歇性跛行的疗效、安全性和成本。
该研究选取了120例患者（纳入109例，99例完成研究）。纳入时平均总步行距离为65.5±8米（范围20 - 109米）。两个方案的第1阶段均为2周的导入期（不治疗）。在LTP中，第2阶段是主要治疗阶段。治疗采用2小时输注（60微克前列地尔α-环糊精，每周5天，共4周）。在第3阶段（4周间隔期），前列地尔α-环糊精每周给药两次（剂量相同）。在第4阶段（从第9周到20周持续3个月的监测期）不使用药物。在STP中，第2阶段分两天进行2小时输注（第1天：上午20微克，下午40微克；第2天上午和下午各60微克）。仅在第一个周期使用减量剂量以评估耐受性降低或副作用。所有其他周期使用全剂量（60微克，每日两次）。在第4周、第8周、第12周开始时重复相同周期（第3阶段）。观察期为第12周到20周（第4阶段）。对于两个方案，在纳入时、每个阶段开始时以及第20周结束时均进行跑步机测试。两组均采用类似的渐进性步行体育训练计划和降低危险因素计划。
意向性分析表明步行距离增加，在第4周（STP为101.5%，LTP为78.3%）、第8周（STP为260.9%，LTP为107.3%）和第20周（STP为351%，LTP为242%）有所改善。两组无痛步行距离有类似增加。未观察到严重的药物相关副作用。LTP中7%的治疗受试者和STP中5%的治疗受试者出现局部、轻度不良反应。LTP的平均成本约为6588欧洲货币单位；STP的平均成本约为1881欧洲货币单位。LTP使步行距离每改善1米的成本为35.6欧洲货币单位，STP为9.45欧洲货币单位（LTP成本的26%；P<0.02）。步行距离平均增加100%时，LTP成本为1937欧洲货币单位，STP为550欧洲货币单位（P<0.02）。前列地尔α-环糊精的成本（包括输注和操作成本）占LTP总成本的25%（STP为24.9%）。
总之，考虑步行距离和成本，组间分析支持STP。结果表明前列地尔α-环糊精治疗具有良好的疗效和耐受性。采用STP时，输注时间减少，可更多地用于运动计划。STP降低了成本，加快了康复进程，可在更多可遵循该方案的非专科单位使用。
