Spinal cord stimulation or prostacyclin in unrevascularizable arteriopathy of lower limbs (SPINAL) study: interim analysis results

摘要

Objective: The aim of this study was to compare the clinical efficacy and the safety of spinal cord stimulation (SCS) plus medical treatment versus iloprost plus medical treatment in patients with severe unrevascularizable ischemia of the lower limbs due to atherosclerotic disease of the limbs and to identify predictive parameters for a positive outcome of SCS.Methods: A multicenter randomized controlled trial (RCT) with central randomization and core laboratory evaluation of angiography, subdivided into two treatment arms (SCS and iloprost) and two subgroups (rest pain and ulcer/gangrene). After the 15-day clinical efficacy evaluation, responder patients continued follow-up in their arm, while nonresponders could change arms or decline participation. The primary endpoint was 1-year limb salvage. Principal secondary endpoints were: survival rate; minor amputations and stump healing; ulcer healing; pain relief and analgesic intake; and predictive criteria for SCS treatment.Results: The trial was stopped at 35.6% of the expected sample due to low accrual rate. Fifty-two patients (55 legs) entered the study. At the 15-day efficacy evaluation, responders (reduced pain, no increase of ulcer area) comprised 74% of the SCS arm and 26% of the iloprost arm, (P=0.003). Nine nonresponders in the iloprost arm underwent SCS implantation. Three severe adverse events (one fatal) were recorded in the iloprost arm and four in SCS treatments. One-year limb salvage rates in SCS, iloprost treatment, and iloprost plus SCS implantation (I-SCS) were 66.8%, 57.1%, and 100%, respectively (P=0.09), and survival rates were 73.2%, 93.9%, and 88.9%, respectively (P=0.45), confirming results of other studies that showed a trend toward better amputation-free salvage in the SCS group. The small number of recruited patients prevented statistical significance being reached. Pain reduction was obtained in 87% of SCS patients and 35% of those in the iloprost arm (P=0.001). Among the examined parameters, only the angiographic resistance index was an independent predictive value of good results after SCS implantation.Discussion and conclusion: The SPINAL study is the first RCT comparing SCS and iloprost. Although incomplete, it evaluated a sample greater than those studied in three out of five available RCTs on SCS. However, the small sample size reduced the statistical power of the study, with possible type II errors. SCS was associated with a quick and more effective answer to pain, with better tolerability and better early results, than iloprost, but without significant 1-year limb salvage-rate improvement. Iloprost improved the 1-year survival in spite of adverse events, and, following these results, perhaps should be administered before other treatments. The results of this trial suggest that prostanoids and SCS are not alternative treatments: as prostanoids present many contraindications and side effects, SCS can be considered the complementary and consecutive treatment for patients who are no longer treatable with open or endovascular revascularizations, and an alternative treatment only in patients with contraindication to prostanoids. The association of iloprost and SCS seems to produce a synergic activity even in patients who had ineffective prostanoid treatment. These results should be confirmed by further investigations in a larger sample.