title: Broad modulation of tissue responses (immune activation) by celacade may favorably influence pathologic processes associated with heart failure progression.
abstract: Immune activation and inflammation contribute to the progression of chronic heart failure (CHF), but therapeutic approaches directed against these processes have been largely unsuccessful. This clinical study evaluated a novel, nonpharmacologic immune modulation therapy, shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines. A total of 75 patients with New York Heart Association (NYHA) functional class III or IV CHF were randomized to receive either Celacade (immune modulation therapy) or placebo (n = 38 and n = 37, respectively) in a double-blind trial for 6 months, during which standard therapy for CHF was maintained. Patients were evaluated using the 6-minute walk test, changes in NYHA class, cardiac function, and quality-of-life assessments, and were observed for the occurrence of death and hospitalization. There was no between-treatment difference in the 6-minute walk test results, but 15 Celacade-treated patients (compared with 9 placebo-treated patients) improved NYHA classification by > or = 1 class (p = 0.140). Kaplan-Meier survival analysis showed that Celacade significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction between groups, but there was a trend toward improved quality of life favoring the Celacade-treated group (p = 0.110). These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of CHF, and they establish the basis for a phase 3 trial to define the benefit of Celacade in CHF.
authors.affiliation: Heart Transplant Service, Methodist DeBakey Heart Center, Baylor College of Medicine, Houston, Texas 77030, USA. gtorre@bcm.tmc.edu
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
authors.forename: François
authors.initials: F
authors.lastname: Sestier
authors.forename: Branislav
authors.initials: B
authors.lastname: Radovancevic
authors.forename: James
authors.initials: J
authors.lastname: Young
mesh_terms: D000368:Aged; D000818:Animals; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome