Broad Modulation of Tissue Responses (Immune Activation) by Celacade May Favorably Influence Pathologic Processes Associated with Heart Failure Progression

• Published in: The American journal of cardiology 2005-06, Vol.95 (11), p.30-37
• Main Authors: Torre-Amione, Guillermo, Sestier, François, Radovancevic, Branislav, Young, James
• Format: Article
• Language: English
• Subjects: Aged; Animals; Biological and medical sciences; Cardiology. Vascular system; Cytokines; Disease Progression; Double-Blind Method; Drug therapy; Female; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - immunology; Heart Failure - mortality; Heart Failure - pathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Immune system; Immunotherapy - methods; Male; Medical sciences; Middle Aged; Pathology; Quality of Life; Survival Analysis; Tissues; Treatment Outcome
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2005.03.010

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 ≥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.