Device-based nonspecific immunomodulation therapy (Celacade), and its potential role in the treatment of chronic heart failure.

Chronic heart failure (CHF) remains a leading cause of mortality and morbidity, despite the use of optimal standard-of-care medical therapies. Although the role of the immune system in the pathogenesis and progression of CHF has been well-appreciated, attempts to modify specific systemic immune mediators have been unsuccessful. Building on the modest successes of more broad-spectrum immune therapies, Celacade therapy was developed, a device that induces apoptosis in an ex vivo blood sample. Upon reinjection into the body, the treated blood sample has been shown to have an anti-inflammatory effect. Celacade has been successful in several animal models of disease where inflammation plays an important pathogenic role. Two phase III clinical trials of Celacade have been undertaken. A trial on the use of Celacade in peripheral arterial disease with intermittent claudication was terminated early due to a lack of clinical effect, and a larger trial of Celacade treatment in CHF (ACCLAIM) was completed in 2006. ACCLAIM did not reach the primary end point for the overall study population; however, the study results demonstrated a reduced risk of death or first cardiovascular hospitalization by 39% in patients with New York Heart Association class II CHF and a 26% reduction in patients with class II, III, and IV disease who had no prior history of myocardial infarction. Celacade has been approved for treatment of CHF in these groups of patients in the European Union, and an FDA-mandated confirmatory study of Celacade for possible approval in the United States is in progress.