Clinical trial NCT00765518: Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
Official title: Intramyocardial Delivery of Autologous Bone Marrow Cells in Patients With Heart Failure Due to Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dilated Cardiomyopathy
Keywords: Ischemic Dilated Cardiomyopathy
Non-Ischemic Dilated Cardiomyopathy
ixmyelocel-T
Lead sponsor: Vericel Corporation
Sponsor class: INDUSTRY
First posted: 2008-10-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 86
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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

Primary outcomes:
measure: Safety will be assessed by: post-procedure assessments, physical exam, vital signs, laboratory tests, and adverse events including MACE (Major Adverse Cardiac Event) occurrences.
timeFrame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12
Secondary outcomes:
measure: Efficacy will be assessed by: MACE, myocardial size, function and perfusion; exercise tolerance, pulmonary function, medication usage, functional status, quality of life, surgical interventions, and blood markers for heart failure
timeFrame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Cleveland
country: United States
facility: Cleveland Clinic Heart and Vascular Institute
state: Ohio
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Methodist DeBakey Heart & Vascular Center
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah School of Medicine
state: Utah
Study officials:
affiliation: University of Utah
name: Amit Patel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henry TD, Traverse JH, Hammon BL, East CA, Bruckner B, Remmers AE, Recker D, Bull DA, Patel AN. Safety and efficacy of ixmyelocel-T: an expanded, autologous multi-cellular therapy, in dilated cardiomyopathy. Circ Res. 2014 Sep 26;115(8):730-7. doi: 10.1161/CIRCRESAHA.115.304554. Epub 2014 Aug 20.