Study of Immune Modulation Therapy in Patients with Symptomatic Peripheral Arterial Disease - SIMPADICO
The goal of the trial was to evaluate treatment with immune modulation therapy compared with placebo among patients with symptomatic peripheral arterial disease.
Patients Screened: 947
Patients Enrolled: 553
Mean Follow Up: 12 months
Mean Patient Age: Mean age 67 years
Change in absolute claudication distance (ACD) from baseline to 26 weeks
Patients were randomized in a double-blind manner to either intramuscular administration of autologous blood treated with controlled oxidative stress (ultraviolet light, oxygen, ozone and increased temperature) (n=262) or placebo (n=273) on days 1, 2, 14, and monthly thereafter. Patients underwent exercise treatmill testing at baseline and follow-up.
Study treatments were terminated 3 months early at the recommendation of the Safety Committee, although total patient enrollment and evaluation of the primary endpoint, which was at 26 weeks, was already completed. The discontinuation was recommended due to an increase in malignancies in the IMT group (5.5% vs 1.1%). Upon further review of these malignancies, 8 were found to have been present at baseline.
Baseline absolute claudication distance was 303 m in the IMT group and 321 in the placebo group. There were no differences in the primary endpoint of change in ACD from baseline (p=0.80). The composite of cardiovascular or peripheral events occurred in 15% of the IMT group and 17% of the placebo group, and mortality in 8 patients and 7 patients, respectively. There was no difference in quality of life scores. C-reactive protein at week 26 was decreased from baseline in the IMT group but not the placebo group. Adverse events other than malignancies did not differ by treatment group.
Among patients with symptomatic peripheral arterial disease, treatment with immune modulation therapy was not associated with a difference in the primary endpoint of change in absolute claudication distance from baseline to 26 weeks compared with placebo.
The increase in malignancies prompted the Safety Committee to discontinue the trial approximately 3 months early. Upon further review, it was determined that many of these malignancies were present prior to entry in the study, a protocol violation. Despite the early discontinuation, no efficacy signal was present for the primary or other endpoints.
Presented by Dr. Jeffrey W. Olin at the March 2006 ACC Annual Scientific Session, Atlanta, GA.
Keywords: Temperature, Follow-Up Studies, C-Reactive Protein, Ultraviolet Rays, Quality of Life, Exercise, Injections, Intramuscular, Oxidative Stress, Peripheral Arterial Disease, Oxygen, Peripheral Vascular Diseases, Ozone
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