use of ixmyelocel-t (formerly cardiac repair cell [crc] treatment) in patients with heart failure due to dilated cardiomyopathy (impact-dcm)

Conditions: Dilated Cardiomyopathy

Summary: this study is designed to assess the safety and tolerability of cardiac repair cells (crcs) compared to standard-of-care in patients with dilated cardiomyopathy (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.

Eligibility criteria:
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

Keywords: ischemic dilated cardiomyopathy non-ischemic dilated cardiomyopathy ixmyelocel-t