Cardiac Repair Cell (CRC) Treatment of Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM) - Full Text View

Sponsored by:	Aastrom Biosciences
Information provided by:	Aastrom Biosciences
ClinicalTrials.gov Identifier:	NCT00765518

Purpose

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).

Condition	Intervention	Phase
Dilated Cardiomyopathy	Biological: Cardiac Repair Cells (CRCs)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Intramyocardial Delivery of Autologous Bone Marrow Cells in Patients With Heart Failure Due to Dilated Cardiomyopathy

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy Heart Failure

U.S. FDA Resources

Further study details as provided by Aastrom Biosciences:

Primary Outcome Measures:

Incidence of major adverse cardiac event (MACE) (MACE defined as: cardiac death, cardiac arrest, myocardial infarction, ventricular tachycardia, ventricular fibrillation, pulmonary edema, acute heart failure, unstable angina and major bleeding) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Left ventricular ejection fraction (to be assessed by cine MRI/cardiac CT and Echocardiography) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Change in LV and RV dimensions and volumes as measured by MRI or cardiac CT and Echocardiography [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Wall Motion Score Index (WMSI) (As determined by MRI/cardiac CT or Tissue Doppler Echocardiography. Regional wall motion at rest will be determined by cine MRI using a 17-segment model to yield the WMSI) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Regional myocardial contractility and maximal elasticity in the dysfunctional segments [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Perfusion (To be assessed by Tc-SPECT in patients with IDCM only. In patients unable to perform physical exercise, adenosine will be used.) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
FDG-PET (Measurements in both IDCM and non-IDCM patients performed to determine myocardial perfusion and metabolism) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Physical exercise capacity (to be determined by the change in distance covered during the 6 minute walk test) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Heart failure symptoms (to be determined by the status and changes documented by measurement of MVO2) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) class (to be determined by the status and change from baseline) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Forced Expiratory Volume in 1 second (status and change as assessed by Spirometry according to ATS/ERS guidelines) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Minnesota Living with Heart Failure Score (MLHFQ) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Incidence of implantation/transplantation of implantable devices (implantable device use determined by percentage of patients undergoing ICD implantation, intraaortic balloon pump implantation, Cardiac Assist Device implantation or heart transplantation) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Heart failure markers (as determined by absolute concentrations and changes to the heart failure markers Troponin I and BNP measured in the peripheral blood) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Heart failure medications (e.g. beta-blockers, ACE inhibitors, Digoxin, Diuretics, Vasodilators, Anti-arrhythmic drugs, and Nitroglycerine) [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: No ]
Assessment of aspiration site throughout study [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Acute post-surgical monitoring of vital signs, special labs and markers, and ECHO [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Assessment of incision site for month following surgery [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Standard chemistry panel including kidney and liver function tests, complete blood count and physical exam, as well as monitoring of vital signs [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Special labs associated with heart function throughout the study, as well as x-ray at 3 mos to evaluate congestion [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Specialized cardiac testing to monitor heart function, i.e., ECG, Holter monitor, ECHO, MRI/CT, SPECT, PET testing [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]
Adverse Event monitoring as well as monitoring specifically for MACE [ Time Frame: Outcome measures will generally be assessed at baseline, Month 1, Month 3, Month 6 and Month 12 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	September 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental The Treatment arm of the study will receive standard of care therapy, a bone marrow aspiration and injections of the study cellular product.	Biological: Cardiac Repair Cells (CRCs) CRCs will be administered via direct injection into the heart muscle.
Control: No Intervention Standard of care therapy only. Patients in the control group may be offered the opportunity to receive CRC treatment in an open label cross-over protocol after completing at least 6 months of treatment. To determine whether this option will be available, the Data Safety Monitoring Board (DSMB) will review safety and efficacy data from the first 20 CRC treatment patients who have completed at least 6 months of follow-up. The DSMB will make a recommendation regarding cross-over CRC treatment for control patients after review of the data and risk benefit profile.

Arms

Assigned Interventions

Treatment: Experimental

The Treatment arm of the study will receive standard of care therapy, a bone marrow aspiration and injections of the study cellular product.

Biological: Cardiac Repair Cells (CRCs)

CRCs will be administered via direct injection into the heart muscle.

Control: No Intervention

Standard of care therapy only. Patients in the control group may be offered the opportunity to receive CRC treatment in an open label cross-over protocol after completing at least 6 months of treatment. To determine whether this option will be available, the Data Safety Monitoring Board (DSMB) will review safety and efficacy data from the first 20 CRC treatment patients who have completed at least 6 months of follow-up. The DSMB will make a recommendation regarding cross-over CRC treatment for control patients after review of the data and risk benefit profile.

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

Ages Eligible for Study:	18 Years to 86 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00765518

Locations

United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
United States, Ohio
Cleveland Clinic Heart and Vascular Institute
Cleveland, Ohio, United States, 44195
United States, Texas
Methodist DeBakey Heart & Vascular Center
Houston, Texas, United States, 77030
Baylor University Medical Center
Dallas, Texas, United States, 75226
United States, Utah
The University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Aastrom Biosciences

Investigators

Principal Investigator:

Amit Patel, MD

University of Utah

More Information

No publications provided

Responsible Party:	Aastrom Biosciences, Inc. ( Elmar R. Burchardt, MD, PhD )
Study ID Numbers:	ABI-55-0712-1
Study First Received:	October 2, 2008
Last Updated:	May 22, 2009
ClinicalTrials.gov Identifier:	NCT00765518 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Aastrom Biosciences:

Ischemic Dilated Cardiomyopathy
Non-Ischemic Dilated Cardiomyopathy

Study placed in the following topic categories:

Heart Failure
Heart Diseases
Dilated Cardiomyopathy
Cardiomyopathy, Dilated

Ischemia
Cardiomegaly
Cardiomyopathies

Additional relevant MeSH terms:

Heart Failure
Heart Diseases
Cardiomyopathy, Dilated

Cardiovascular Diseases
Cardiomegaly
Cardiomyopathies

ClinicalTrials.gov processed this record on July 02, 2009