Safety Study of AMI MultiStem® to Treat Heart Attacks

NCT ID: NCT00677222

Last Updated: 2012-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2012-02-29

Brief Summary

The purpose of this study is to determine if escalating doses of AMI MultiStem® delivered by catheter can safely be given to patients that have had a recent heart attack treated with stent implantation.

Detailed Description

The mortality rates associated with acute myocardial infarction (AMI) have significantly decreased over the past 2 decades. Beginning first with thrombolytic therapy for AMI, and more recently with growing acceptance and availability of primary percutaneous coronary intervention (PCI) for ST-elevation AMI, the mortality rates of this devastating ischemic event have decreased from almost 15% in clinical trials in the late 1980's to <5% in recent primary percutaneous coronary intervention trials. Though AMI-related mortality has been reduced, AMI survival is often accompanied by significant loss of function that may lead to subsequent treatments, congestive heart failure (CHF) and reduction in quality of life. A cell therapy that could reduce the damage associated with AMI and positively affect heart function would provide substantial benefits to the AMI patient.

Conditions

Acute Myocardial Infarction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Treatment arm

Group Type: EXPERIMENTAL

AMI MultiStem®

Intervention Type: BIOLOGICAL

AMI MultiStem® administered via catheter into peri-vascular space of the target vessel, 2-5 days post PCI. There will be 3 dose escalation cohorts, 6 patients per cohort.

2

Registry Arm -standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

AMI MultiStem®

AMI MultiStem® administered via catheter into peri-vascular space of the target vessel, 2-5 days post PCI. There will be 3 dose escalation cohorts, 6 patients per cohort.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients of either sex 18-85 years of age
• Women of childbearing potential or less than 2 years postmenopausal agree to use of adequate contraception during the study
• Patients with the first time diagnosis of ST elevation myocardial infarction
• Acute myocardial infarction (ST elevation in at least two leads >0.2 mV in V1, V2 or V3 or >0.1 mV in other leads), treated by one of the following: either
• Acute PCI with stent implantation
• With thrombolysis within 12 hr of symptom onset followed by PCI with stent implantation within 24 hr after Thrombolysis
• Maximal creatine kinase elevation >400 U/l with significant membrane-bound fraction (>6%)or troponin >2X ULN
• Decreasing levels of CK/CK-MB or troponin following reperfusion
• Successful acute PCI/stent implantation (residual stenosis visually <30% and TIMI flow >2). Absence of severe disorder of the microcirculation (e.g. pulsatile flow pattern, systolic flow reversal) at the time of administration of the trial therapy
• Significant regional wall motion abnormality in left ventricular angiogram or transthoracic echocardiogram ≤48 hours post PCI
• LVEF between 30 and 45% by LV gram after the primary PCI or transthoracic echocardiogram ≤48 hours post PCI
• Willing and able to comply with the scheduled visits, treatment, laboratory tests and other study related procedures.
• Signed informed consent

Exclusion Criteria

• Prior cardiovascular history
• Mechanical complications of the index acute myocardial infarction including but not limited to rupture of the mitral valve with resultant development of mitral regurgitation, rupture of the left ventricular free wall and rupture of the interventricular septum
• Pregnant or lactating
• Known allergy to contrast agents
• Known allergy or religious objections to bovine or porcine products
• History of malignancy of any type except non-melanoma skin cancer
• Presence of major hematological conditions or laboratory abnormalities (low hemoglobin (<10 gm/dl), - WBC (<3,000 cells/mm2) or platelet count (<100,000 cells/mm3))
• Prothrombin time (PT) > 1x ULN
• Partial thromboplastin time (PTT) > 1x ULN
• Presence of chronic systemic inflammatory disorders that requires ongoing therapy
• Previous autologous, allogeneic bone marrow or peripheral stem cell transplant
• Prior solid organ transplantation
• Immune system compromise including but not limited to history of human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) infection.
• Prior participation in any other study involving investigational pharmacological agents(s), devices or marketed products within 30 days prior to planned AMI MultiStem® administration
• Life expectancy of six months or less
• Current alcohol or substance abuse
• Ongoing systemic infection
• Renal function: Serum creatinine >2 mg/dL or creatinine clearance ≤50 mL/min
• Hepatic function: Screening ALT and AST ≥3x upper limit of normal for the laboratory or total bilirubin ≥2.0 mg/dL (exception: acceptable if patient is identified with pre existing condition e.g. Gilbert's disease that will contribute to baseline elevations of bilirubin)
• Other serious medical or psychiatric illness that, in the investigator's opinion, would not permit the patient to be managed according to the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

Angiotech Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Healios K.K.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Penn, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Warren Sherman, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Cardiology PC

Birmingham, Alabama, United States

The Care Group

Indianapolis, Indiana, United States

Henry Ford Hospital

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Metro Health

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Hamot Medical Center

Erie, Pennsylvania, United States

Countries

United States

References

Penn MS, Ellis S, Gandhi S, Greenbaum A, Hodes Z, Mendelsohn FO, Strasser D, Ting AE, Sherman W. Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study. Circ Res. 2012 Jan 20;110(2):304-11. doi: 10.1161/CIRCRESAHA.111.253427. Epub 2011 Nov 3.

Reference Type: DERIVED

PMID: 22052917 (View on PubMed)

Other Identifiers

AMI-07-001

Identifier Type: -

Identifier Source: org_study_id