Advanced Chronic Heart Failure Clinical Assessment Of Immune Modulation Therapy

# Complete Title of Study
A Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Assess the Effects of the CelacadeTM System on Mortality and Morbidity in Patients With Chronic Heart Failure

# Study Acronym (The trial's abbreviation if there is one)
ACCLAIM

# Principal Investigator, Co-investigators, and Collaborating Institutions
Study director: Andrea B Parker, PhD
Institution: Vasogen Inc.

# Overview of Trial
The goal of the study was to test the safety and efficacy of the CelacadeTM system in reducing the risk of mortality and cardiovascular hospitalizations in patients with chronic systolic heart failure.

# Disease State(s) Studied (e.g. acute MI, breast cancer, etc.)
Heart failure, congestive

# Study Phase (e.g. Phase I,II,III,IV) Study Phases are defined here
Phase III

# Study Design (e.g. multicenter, randomized, double blind, placebo controlled)
Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

# Study Arms and How They Were Treated (Intervention) (Explanation here)
2,016 patients were randomized to either placebo or an immune modulation therapy device (the CelacadeTM system).

# Primary Pre-Specified Endpoints
- Mortality
- Cardiovascular hospitalization

# Secondary Endpoints
- Clinical status
- Health-related patient quality
- Healthcare resource utilization

# Inclusion Criteria
- Male or female aged 18 or older.
- New York Heart Association (NYHA) Class II to IV.
- Left ventricular ejection fraction (LVEF)  30%, measured within the past six months (by any technique), unless there was a cardiovascular event that could have modified the LVEF during that period (e.g., coronary artery bypass grafting , myocardial infarction ). If the patient was started on a beta-blocker or biventricular pacing (cardiac resynchronization therapy, or CRT), the LVEF measurement must have been at least three months after starting the therapy.
- Hospitalized for heart failure; OR, received intravenous (IV) administration of an inotropic agent (therapeutic dose for HF), human B-natriuretic peptide, or IV diuretic (minimum 40 mg of furosemide or equivalent) in a clinic, outpatient or emergency department within the past 12 months (stable for at least 2 weeks). Exceptions: patients in NYHA Class III or IV who have a LVEF of < 25%.
- On standard therapy for congestive heart failure (CHF), which must include angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blocker (ARB) (unless contraindicated or patient is intolerant), with or without other appropriate agents. If on a beta-blocker, patient must have been on a beta-blocker for at least three months.
- No changes in active cardiac medications for heart failure during the two weeks prior to randomization.
- Written informed consent.

# Exclusion Criteria
- Inability to comply with the conditions of the protocol.
- Presence of a transplanted tissue or organ or left ventricular assist device (LVAD) (or the expectation of the same within the next 12 months).
- Planned Automatic Implantable Cardiac Defibrillator (AICD) or CRT within the next 12 months.
- Acute MI, or CABG, percutaneous coronary intervention (PCI), AICD, or CRT within the past three months.
- Need for chronic intermittent inotropic therapy.
- Malignancy: evidence of disease within the previous five years. Exceptions: basal cell carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in situ of the cervix.
- Active myocarditis or early postpartum cardiomyopathy (within the first six months of delivery).
- Systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment.
- Pregnancy, or patients of childbearing potential not using adequate contraceptive methods.
- Porphyria.
- Allergy to sodium citrate or any caine type of local anesthetic.
- Previous CelacadeTM treatment.
- Patient scheduled for hospice care.
- Clinically relevant abnormal findings in the clinical history, physical examination, electrocardiogram (ECG), or laboratory tests at the screening assessment that would interfere with the objectives of the study or that would, in the investigators opinion, preclude safe completion of the study.
Abnormal findings could include: known HIV infection or other immunodeficiency state, chronic active viral infection (such as hepatitis B or C), acute systemic infections (defined as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding, or any severe or acute concomitant illness or injury.
- Any other medical, social, or geographical factor that would make it unlikely that the patient could comply with study procedures (e.g., alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location, or a history of noncompliance).

# Outcome: Primary endpoint (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

# Outcome: Secondary endpoint (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

# Outcome: Exploratory endpoints (Report both relative risk reduction and absolute risk reduction as well as number needed to treat if available)
None reported

# Outcome: Safety endpoints (Report both relative risk and absolute risk as well as number needed to harm if available)
None reported

# Conclusions of the Investigators (Quote the investigators conclusions here)
None reported

# Commentary, Discussion and Limitations of the Trial (Anyone can add comments)
None reported

# Slides
None reported

# Video Commentary
None reported

# References (How to insert a reference)
None reported

# External sites for further information (How to insert links)
Torre-Amione G, Anker SD, Bourge RC, Colucci WS, Greenberg BH, Hildebrandt P, Keren A, Motro M, Moye LA, Otterstad JE, Pratt CM, Ponikowski P, Rouleau JL, Sestier F, Winkelmann BR, Young JB; Advanced Chronic Heart Failure CLinical Assessment of Immune Modulation Therapy Investigators. Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial. Lancet. 2008 Jan 19;371(9608):228-36.

# Detailed information about the trial
Evidence continues to accumulate on the importance of inflammation in the development and progression of heart failure (HF). The CelacadeTM system may reduce chronic inflammation by stimulating the immune systems physiological anti-inflammatory response. The ACCLAIM study is an international, approximately 2,000-patient, Phase III clinical research study designed to test the safety and efficacy of the CelacadeTM system in reducing the risk of mortality and cardiovascular hospitalizations in patients with chronic systolic HF.

# Ages
18 years and older

# Gender (Indicate whether men, women or both were enrolled)
Both men and women were eligible for the study

# Accepts Healthy Volunteers (Answer yes or no)
No

# Enrollment Period (Study start and end date)
Study start date: June 2003
Estimated study completion date: November 2005

# Recruitment Status (explanation)
Study has been completed.

# Enrollment (Total number of patients enrolled)

# Study Sponsor (e.g. Investigator initiated or company name)
Vasogen

# Source of Data (Where is this data on this page coming from: publication, principal investigator, or co-investigator)
The content of the clinical trial wiki consists of fields that have been suggested by the World Health Organization and wwww.clinicaltrials.gov.