Rationale and methodology of the ICAI study, a randomised clinical trial of alprostadil in the treatment of chronic critical leg ischemia

Abstract: Objective: to evaluate the safety and efficacy of a stable prostaglandin E(1) added to the usual therapeutic practice (either invasive or not) in patients with chronic critical leg ischemia. Design: multicenter, controlled, randomised, open label trial. Setting: a representative sample (56 centers) of vascular and general surgery, angiology and general medicine departments of the Italian National Health Service. Patients: all patients suffering from leg ischemia considered as chronic and critical depending on the presence of persistently recurring rest pain for more than two weeks and/or foot ulceration or gangrene. Intervention: a daily i.v. infusion of 60 mu g of alprostadil alpha-cyclodextrine for the overall hospital stay, up to a maximum of 28 days (as an adjunct to the standard procedures adopted In each center) to patients randomly assigned to the experimental treatment. Measures: the primary evaluation of efficacy is based on the expected reduction of major amputations or persistence of critical leg ischemia at six months, The sum of these ''peripheral'' events, of death and of non-fatal myocardial infarction and stroke is used as a more comprehensive evaluation of the risk/benefit profile of the experimental treatment. Results: a reduction from 40% to 32% of the incidence of the primary end-points is the trial hypothesis, The recruitment of 1500 patients is required to verify this. Conclusions: this large-scale trial aims at providing a reliable estimate of the possibility of modifying hard end-points such as death and amputation in patients with critical leg ischemia.