Heparan sulfate in the treatment of intermittent claudication: results of a randomized, double-blind, placebo-controlled multicenter trial.

Peripheral arterial disease (PAD) is by far the most common cause of intermittent claudication. This disease can greatly reduce the affected individual's walking capacity and can seriously affect daily life activities. Few therapeutic options are aimed at improving walking capacity. This was a randomized, doubleblind, placebo-controlled, multicenter trial, performed in 24 Italian centers. Two hundred seventeen patients with intermittent claudication (stages IIa and IIb of Fontaine's PAD classification) were randomly assigned to heparan sulfate (40 mg orally twice a day) or placebo for 6 months. The primary end-point was an increase in pain-free walking distance [initial claudication distance (ICD)] during the 24 weeks of treatment. The pain-free and the absolute walking distance (ACD) were monitored by standardized treadmill test at baseline and at 4, 12 and 24 weeks. The change in initial claudication distance during treatment, expressed as integrated change over time, was significantly greater with heparan sulfate than with placebo (306 +/- 494 vs. 250 +/- 510 meters x months, p = 0.019). Significantly fewer treated patients worsened during treatment (decreased initial claudication distance) compared with controls (9.1% vs. 19.6%; p = 0.027). Functional recovery in the most severely affected subgroup of patients (stage IIb of Fontaine's classification) was more clearly detected and significantly greater among treated than among control patients (absolute increase in ICD: 70 +/- 113 vs. 58 +/- 172 meters, p = 0.028; integrated increase: 304 +/- 422 vs. 208 +/- 503 meters x months; p = 0.004). Heparan sulfate appeared to increase the walking capacity of patients with intermittent claudication to a significantly greater extent than did placebo. The treatment was well tolerated.