World Congress of Cardiology Report - Heart failure (HF) is a complex, progressive clinical syndrome that can result from any structural or functional cardiac disorder, such as coronary artery disease or hypertension (high blood pressure), which impairs the ability of the heart to function properly as a pump.
As a result of this pump dysfunction, a variety of body mechanisms are activated in an attempt to compensate for this defect. Multiple systems within the body, including the neurohormonal system and the immune system, respond to the HF state. Accumulating evidence indicates that inflammatory cytokines (immune response mediators) play a pathogenic role in the progression of HF by impairing the ability of the heart to contract, inducing excessive hypertrophy (enlargement), and promoting cell death or fibrosis (the formation of fibrous tissue). These mechanisms contribute to the destructive cycle of myocardial (heart muscle) remodeling that is characteristic of chronic heart failure.
The primary objective of the ACCLAIM study was to evaluate the effects of Celacade immunotherapy on the composite endpoint of mortality or cardiovascular (CV) hospitalization in patients with chronic HF. ACCLAIM stands for Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy.
Immunotherapy using the Celacade System is a novel non-drug treatment strategy that targets inflammatory mechanisms contributing to progression of chronic HF not yet addressed by current therapies. This form of immunotherapy exploits the anti-inflammatory response to cells undergoing apoptosis (programmed cell death). The physiological response of the recipient's immune system to apoptotic cells results in a decrease in inflammatory cytokines, and up-regulation of anti-inflammatory cytokines. This combined effect may be especially beneficial to patients with chronic HF, since the inflammation associated with this syndrome reflects an imbalance of the two opposing arms of the cytokine network.
Celacade immunotherapy has been shown experimentally to down-regulate pro-inflammatory cytokines and increase anti-inflammatory cytokines. We have previously shown, in a feasibility study of subjects with moderate to severe HF, that active treatment significantly reduced mortality and hospitalization. Moreover, in a recently completed study of 553 patients with atherosclerosis, this form of immunotherapy resulted in a marked reduction in the inflammatory marker hs-CRP.
The ACCLAIM study enrolled over 2,400 subjects at 177 sites in the US, Canada, Germany, Norway, Denmark, Poland, and Israel. ACCLAIM was the largest trial in HF ever conducted to evaluate a therapy targetting inflammation. At baseline, all subjects were receiving optimal standard therapy for HF including ACE inhibitors or angiotensin receptor blockers, beta-blockers, and aldosterone blocking agents as tolerated.
Immunotherapy using the Celacade System involves the ex vivo (outside the body) treatment of a 10mL sample of a patient's own (autologous) whole blood with controlled oxidative stress and subsequent intramuscular (IM) administration of the treated sample. We hypothesize that oxidative stress, a factor known to initiate apoptosis in white cells, commits the treated cells to undergo apoptosis following IM administration. Within the muscle tissue, the treated cells interact with specific immune system cells (antigen presenting cells) and elicit a systemic anti-inflammatory response.