Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial. Intermittent intraarterial infusion therapy with PGE1 in patients with severe claudication--results of a randomized prospective double blind study. A randomized trial of iloprost in patients with intermittent claudication. Clinical and haemorheological efficacy of i.a. PGE1 infusions in intermittent claudication. Impact of a 4-week treatment with prostaglandin E1 on health-related quality of life of patients with intermittent claudication. Pharmacologic treatment of intermittent claudication. Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. The effects of prostaglandin E-1 in patients with intermittent claudication. Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.
For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication. In a randomized prospective double blind study, intraarterial infusion therapy with prostaglandin E1 (PGE) was tested against infusion therapy with energy rich phosphates (ERP) in 40 patients with severe claudication. During the treatment period of three weeks, a significant increase of the painfree (PWD) and maximal walking distance (MWD) was observed. The improvement of PWD was of clinical relevance (PGE: 60----195 m; ERP: 69----170 m; p less than 0.001) and persisted during a 36 week post treatment observation period. The differences between the two drugs were not significant but showed a tendency in favour of the PGE therapy. Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 microg, 100 microg, or 150 microg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 microg, 100 microg, and 150 microg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication. nan Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity. The aim of this study was to evaluate the effects of a 4-week treatment with prostaglandin E1 (PGE1), a drug inducing vasodilation and inhibiting platelet aggregation, on improving functional status and health-related quality of life in patients with disabling intermittent claudication. Forty-two untrained outpatients (37 men and five women, mean age 64 +/- 8 years) with intermittent claudication,and maximum walking distance (MWD) of at least 50 and no more than 200 m on treadmill test (5% slope, 3 km/hr) were randomized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours (21 patients) or placebo (250 mL saline, 21 patients). Treatment-free follow-up was completed 8 weeks after the final infusion. Pain free walking distance (PFWD), MWD, and questionnaire evaluation were determined at baseline, after the 4-week treatment period, and at the end of the 8 weeks of the treatment-free follow-up period. After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 +/- 16 m to 135 +/- 33 m (+87%, p<0.001)and from 140 +/- 30 m to 266 +/- 62 m (+90%, p<0.001), respectively. Analysis of the Walking Impairment Questionnaire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score (+19 percentage points, p<0.001), in the distance score (+25 percentage points, p<0.001), in the speed score (+24 percentage points, p<0.001), in the stair climbing score (+20 percentage points, p<0.001). The RAND survey responses showed improvements in physical function and bodily pain scores (+14 percentage points, p<0.001, and +15 percentage points, p<0.01, respectively). After the treatment-free follow-up period of 8 weeks, increases in PFWD and MWD were maintained (113 +/- 26 m, +57%, p<0.001, and 229 +/- 55 m, +63%, p<0.001, respectively). Similarly, at the end of the treatment-free follow-up, the walking impairment score (+16 percentage points, p<0.001), the distance score (+23 percentage points, p<0.001), the speed score (+22 percentage points, p<0.001), the stair climbing score (+18 percentage points, p<0.001) as well as the RAND physical function and bodily pain scores (+10 percentage points, p<0.001, and +13 percentage points, p<0.01, respectively) were still increased compared with baseline. No change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period. These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients. The improvements are also maintained for a period of 8 weeks beyond the end of the treatment. Additional studies are needed to determine the duration of functional benefits after the end of treatment. Twenty-six patients with severe short-distance claudication underwent a 24-week, randomized, double-blind, parallel-group evaluation of the efficacy of pentoxifylline in the treatment of intermittent claudication. The primary variables analyzed were the initial and absolute claudication distances as determined by standardized treadmill walking. A statistically significant improvement in both parameters was present in the pentoxifylline-treated patients. Nausea was the only drug side effect noted. The efficacy, safety, and tolerance of pentoxifylline (Trental, Hoechst-Roussel Pharmaceuticals, Inc.) in the treatment of intermittent claudication associated with chronic occlusive arterial disease (COAD) were evaluated in a double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving a total of 128 outpatients. The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a standardized treadmill test. Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD. Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients. These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD. White the precise mode of therapeutic action requires clarification, pentoxifylline was well tolerated with minimal unwanted effects. Aim of the study is to evaluate the effects of Prostaglandin E-1 (PGE-1) in patients with peripheral arterial disease (PAD) at the 2nd b stage Fontaine's classification. The study, controlled, single blinded, enrolled 123 patients with intermittent claudication that were randomised in two groups; the first group received a treatment with PGE-1 while the second one received a pentoxifylline-buflomedil association by venous infusion. We evaluated: Pain Free Walking Distance (PFWD), Maximum Walking Distance (MWD), Rest Flow (RF), Peak Flow (PF), Basal (BVR) and Minimal Vascular Resistance (MVR) with a strain gauge plethysmograph, Resting Flow (RF), Peak Flow (PF), time to reach the Peak Flow (tPF) and time to recovery of the base values (tRF) with laser Doppler flowmeter. After a four weeks treatment, we observed an increase of 370% about PFWD and of 260% in the MWD in patients treated with PGE-1; the other group showed an increase of 110% and 118% respectively. Moreover, the patients of the first group showed a significant increase regarding the plethysmographic Peak Flow (from 9.75+/-1.37 to 16.21+/-1.75, p<0.001), greater than the one observed in the second group (from 9.53+/-1.41 to 13.47+/-1.53, p<0.05); also the laser Doppler parameters showed a significant reduction, more evident in the first group (tPF from 23.0+/-7.5 to 10.5+/-4.9, p<0.001; tRF from 73.5+/-22.7 to 48.3+/-13.5, p<0.001) than in the second one. to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. Design: prospective, randomised study.
                a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis.
                invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure.
                invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.
                Copyright 2001 Harcourt Publishers Limited.
Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question.