Device-Based Nonspecific Immunomodulation Therapy (Celacade), and Its Potential Role in the Treatment of Chronic Heart Failure

Abstract

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.

Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases

“…Moreover, a failure has not been restricted to the SIMPADICO trial performed in 533 patients with symptomatic PAOD [18] but it has included the successive ACCLAIM multicenter, double-blind placebo controlled study based on using an extremely ozone-oxidized blood (107.5 mg ozone per ml of blood) plus an undetermined UV irradiation and heat exposure at 42.5 °C which was thought to display an immune suppressive activity able to abolish the chronic heart inflammation [19]. This rationale has been severely criticized [20][21][22][23][24] and it is hoped that physicians will not privately use this approach.…”

Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies

“…Subsequently, celacade has been approved for use in the European Union for the treatment of HF in all NYHA class II patients and in classes II, III, and IV patients with no prior history of myocardial infarction. 131 , 132 …”

The irrationality of a non-specific immunomodulation therapy used in cardiovascular diseases deserves a critical comment

“…Sliwa and Ansari [10] pointed out several potential problems but did not comment the wrong oxidative technology. An intermediate position of wait and see has been concurrently adopted by Sporter [11]. On the other hand, one of us [12,13] made specific criticism regarding the irrational technology and deeply dissented with Vasogen's (since October 2009 merged in IntelliPharmaceutics International Inc.) hypothesis.…”