Clinical trial NCT00526253: To Assess Safety and Efficacy of Myoblast Implantation Into Myocardium Post Myocardial Infarction
Official title: A Multicenter Study to Assess the Safety and Cardiovascular Effects of Myocell™ Implantation by a Catheter Delivery System in Congestive Heart Failure Patients Post Myocardial Infarction(s)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Congestive Heart Failure
Keywords: Congestive Heart Failure
CHF
Heart Disease
Heart Attack
Stem Cell
Myoblast
Bioheart
Lead sponsor: Bioheart, Inc.
Sponsor class: INDUSTRY
First posted: 2007-09-10
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study injects a person's own stem cells into heart muscle tissue after a person has one or more heart attacks. The purpose of the study is whether the stem cells will improve a patient's heart performance.

Detailed description: Autologous myoblasts are harvested from a patient's skeletal muscle tissue. The myoblasts are isolated and expanded in culture in a closed system. When a sufficient number of cells are estimated they are taken from culture, packaged in a suspension and sent to the patient's interventionalist. The interventionalist uses an injection catheter via femoral artery to inject the myoblasts directly into the myocardium.

Eligibility criteria: Inclusion Criteria:

Eligible patients must meet ALL of the following inclusion criteria during the screening/enrollment visit #1 and prior to being randomized into the study. Screening/enrollment visit #1 is defined to start the date the ICF is signed by the patient:

1. Chronic CHF, New York Heart Association (NYHA) Class II-IV;
2. Stable and on optimal medical management for greater or equal to 60 days as follows:

   1. systolic and diastolic hypertension controlled in accordance with contemporary guidelines;
   2. patient stabilized on maximum tolerated dose of beta blockers;
   3. patient stabilized on maximum tolerated dose of angiotensin concerting enzyme (ACE) inhibitors;
   4. patients intolerant of ACE inhibitors should be stabilized on angiotensin receptor blockers (ARB);
   5. fluid control with diuretics and a salt restricted diet;
   6. patients with sever symptoms of heart failure (Class III-IV) lacking contraindications to aldosterone antagonism and not on both ACE inhibitors and ARBs have been considered for such therapy.
3. Age 18-80;
4. Left ventricular ejection fraction (LVEF) at screening of less than or equal to 35 percent by multiple gaited acquisition scan (MUGA);
5. Need or feasibility for revascularization has been ruled out by previous coronary angiogram or ruled out to the satisfaction of the investigator via previous conventional stress study completed within 1 year of screening. The need or feasibility for revascularization will be reassessed at screening using dobutamine stress echocardiography (DSE);
6. Defined region of mycardial dysfunction related to previous MI involving the anterior, later, posterior or inferior walls including the apical septum (excluding the basal septum) assessed by a large area of akinesia in the left ventricle (using DSE at screening);
7. B-type natriuretic peptide (BNP) or NT pro-BNP is above the upper limit of normal.

Exclusion Criteria:

1. Non-pregnant women who are not postmenopausal, surgically sterile or not practicing an acceptable method of contraception. A female patient of child bearing potential, with a positive serum or urine pregnancy test at screening visit #1. Females refusing to exercise a reliable form of contraception;
2. Myocardial wall thickness of \<6 mm (millimeters) in the akinetic myocardial region to be injected (using DSE at screening)
3. Inability to undergo a surgical biopsy of the skeletal muscle for culture of myoblasts, including any significant myopathy;
4. Patient will require revascularization within six months;
5. Patients on continuous or intermittent intravenous drug therapy;
6. Not fitted, or fitted within less than 90 days prior to screening visit #1, with an implantable cardioverter defibrillator (ICD);
7. Sustained ventricular tachycardia (VT), automatic implantable cardiodefibrillator (AICD) firing, or ventricular fibrillation (VF) within 90 days prior to screening visit #1;
8. Inability to perform a 6 minute walk test due to physical limitations other than HF including:

   1. Severe peripheral vascular disease, including aortic aneurysms, leading to limited claudication;
   2. Severe pulmonary disease or chronic obstructive pulmonary disease (COPD) limiting exercise, dependence on chronic oral steroid therapy or previously requiring mechanical ventilation;
   3. Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to screening visit #1;
9. MI, unstable angina or percutaneous coronary intervention (PCI) within 90 days prior to screening;
10. having undergone CABG surgery within 150 days prior to screening visit #1;
11. Active myocarditis, constrictive pericarditis, restrictive, hypertrophic or congenital cardiomyopathy;
12. Hemodynamically significant severe primary valvular heart disease, unless corrected by a properly functional prosthetic valve;
13. Prior aortic valve replacement;
14. Systolic blood pressure (supine) ≤90 mmHg;
15. Resting heart rate \>100 bpm;
16. Severe uncontrolled HF including any evidence of severe fluid overload such as peripheral edema \>+2 or rales ≥1/3 the lungs' height, need for intravenous therapy for HF within 60 days of screening visit #1 or hospitalization for HF within 90 days of screening visit #1;
17. Patient scheduled to receive cardiac resynchronization therapy (CRT) during the study;
18. Expected to receive or received a cardiac transplant, surgical remodeling procedure, left ventricular assist device or cardiomyoplasty;
19. Six-minute walk test (6MWT) of \>400 meters or Minnesota Living With Heart Failure (MLWHF) score of \<20;
20. Hematocrit (HCT) concentration below 30% (males) or below 27% (females);
21. Serum creatinine greater than 2.5 mg/dL (milligrams per deciliter) or end stage renal disease;
22. Left ventricular mural thrombus;
23. Known sensitivity to gentamicin sulfate; or severe adverse reaction to nonionic radiocontrast agents;
24. Active infectious disease and/or known to have tested positive for human immunodeficiency virus (HIV), human t lymphotrophic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV); immunoglobulin M \[IgM\], and/or syphilis. If the panel includes antibodies to the HBV core antigen (HBV-cAg) and hepatitis B surface antigen (HBV-sAg), then an expert will be consulted as to patient's eligibility based on the patient's infectious status;
25. Patients have undergone enhanced external pulsation (EECP) tratment within the last 6 months;
26. Exposure to any previous experimental angiogenic therapy and/or myocardial laser therapy, or therapy with another investigational drug within 60 days of screening visit #1 or enrollment in any concurrent study that may confound the results of this study;
27. Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate;
28. Any illness other than CHF which might reduce life expectancy to less than 1 year from screening visit #1;
29. Recent initiation of cardiac resynchronization therapy via placement of a bi-ventricular pacemaker or bi-ventricular AICD within 180 days of study enrollment; and

30 Unwilling and/or not able to give written informed consent.

Primary outcomes:
measure: 6-minute walk test
timeFrame: 6 months
measure: Quality of Life Questionnaire
timeFrame: 6 months
Secondary outcomes:
measure: Hospitalization occurrences
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Gilbert
country: United States
facility: Mercy Gilbert Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Heart Institute
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Fort Lauderdale
country: United States
facility: Jim Moran Heart and Vascular Research Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Shands
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Center Cardiovascular Center
state: Florida
city: Atlanta
country: United States
facility: Emory/Crawford Long
state: Georgia
city: Atlanta
country: United States
facility: St. Joseph's Research Institute/ACRI
state: Georgia
city: Chicago
country: United States
facility: RUSH University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Camden
country: United States
facility: Our Lady of Lourdes Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Gagnon Heart Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospital, Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: Stern Cardiology
state: Tennessee
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
References: