Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)

Heart failure remains a major public health problem, affecting 5 million patients in the US with 550,000 new diagnoses made each year. Heart failure is the leading cause of hospitalization in persons over 65 years of age with cost exceeding $29 billion annually. Prognosis is very poor once a patient has been hospitalized with heart failure. The mortality risk after heart failure hospitalization is 11.3% at 30 days, 33.1% at 1 year and well over 50% within 5 years (Hunt SA; et al., 2005). These numbers emphasize the need to develop and implement more effective treatments to manage heart failure.

This study is targeting a subset of heart failure patient population, namely those diagnosed with dilated cardiomyopathy (DCM). The World Health Organization (WHO) defines dilated cardiomyopathy as a cardiac condition wherein a ventricular chamber exhibits increased diastolic and systolic volume and a low (<40%) ejection fraction. DCM is reported to affect 108,000 to 150,000 patients in the U.S.

This study is a prospective, stratified, randomized, open-label, controlled, multi-center study to assess the safety profile and efficacy of CRCs in treating patients with DCM. It will enroll a total of 40 patients at 5 sites in the U.S.

Inclusion criteria

• Diagnosis of ischemic or nonischemic DCM according to World Health Organization criteria; OR ischemic DCM (DCM in a patient with a history of myocardial infarction or evidence of clinically significant (>/= 70% narrowing of a major epicardial artery) coronary artery disease)
• No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, in the opinion of the investigator and the referring interventional cardiologist
• Left ventricular ejection fraction </= 30% by echocardiogram
• Symptomatic heart failure in NYHA functional class III or IV
• Able to comply with scheduled visits in cardiac out-patient clinic
• Able to tolerate study procedures, including bone marrow aspiration, left lateral thoracotomy or thoracoscopy with single lung ventilation, MRI or cardiac CT, spirometry and 6 minute walk test
• Males and females, 18-86 years of age
• Life expectancy of 6 months or more in the opinion of investigator
• Able to give informed consent
• Normal organ and marrow function (Leukocytes >/= 3,000/microgram, Absolute neutrophil count >/= 1,500/microgram, Platelets >/= 140,000/microgram, AST (SGOT)/ALT (SGPT) </= 2.5 x institutional standards range) and Creatinine </= 2.5 mg/dL)
• Adequate pulmonary function (forced expiratory volume in one second [FEV1] > 50% predicted)
• Controlled blood pressure (systolic blood pressure </= 140; diastolic blood pressure </= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study
• Adequate medical management of DCM and other pre-existing conditions. Drug treatment regimen must have been established for at least a month prior to randomization in eligible patients.
• Fertile patients must agree to use an appropriate form of contraception while participating in the study

Exclusion criteria

• Severe primary valvular insufficiency(ies)
• Known history of Chronic Obtrusive Pulmonary Disease (Gold stages IIB or more severe only) or restrictive pulmonary disease
• Known history of primary pulmonary hypertension
• Ventricular Assist Device implantation
• Myocardial infarction within 4 weeks of randomization
• Life-threatening ventricular arrhythmia, except if implantable cardioverter defibrillator is implanted
• Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration
• Patients receiving treatment with hematopoietic growth factors
• Patients who require uninterruptible anticoagulation or anti-platelet therapy [i.e. anticoagulation therapy (e.g. warfarin) that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections]
• Patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and intramyocardial injections
• Known cancer and undergoing treatment including chemotherapy and radiotherapy
• Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 6 months after surgery
• End stage renal disease requiring dialysis
• Patients pregnant or lactating; positive for hCG
• History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz [360mL] of beer or 1.5 oz [45mL] of hard liquor) or history of illicit drug use within 6 months of screening
• Known allergies to protein products (horse or bovine serum, or porcine trypsin)
• Body Mass Index of 40 Kg/m2 or greater
• Patients receiving experimental medications or participating in another clinical study within 30 days of screening
• HIV or syphilis, positive at time of screening
• Active Hepatitis B, or Hepatitis C infection at time of screening
• In the opinion of the investigator, patient is unsuitable for cellular therapy
• Patients receiving anti-angiogenic drugs