[European trial of PGE1 alpha cyclodextrin. Short-term vs. long-term therapy in intermittent claudication].
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Laurora
G
G
Angiology and Vasc. Surgery, Clinical Trials Unit, Pierangeli Clinic, Pescara.
Corsi
M
M
Bucci
M
M
Cesarone
M R
MR
Belcaro
G
G
Dugall
M
M
D000527:Alprostadil / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D008297:Male; D013997:Time Factors
D003505:Cyclodextrins; D000527:Alprostadil