Safety Study of AMI MultiStem® to Treat Heart Attacks
Primary Purpose
Acute Myocardial Infarction
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMI MultiStem®
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myocardial Infarction focused on measuring Acute Myocardial Infarction, Heart Attack
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.
Sites / Locations
- Cardiology PC
- The Care Group
- Henry Ford Hospital
- Columbia University Medical Center
- Metro Health
- Cleveland Clinic
- Hamot Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
1
2
Arm Description
Treatment arm
Registry Arm -standard of care
Outcomes
Primary Outcome Measures
Assessment of adverse events during the first 24 hours after administration of AMI MultiStem® and post acute adverse events up to 30 days following AMI
Secondary Outcome Measures
Evaluation of longer term safety and cardiac function over 12 months following AMI
Full Information
NCT ID
NCT00677222
First Posted
May 12, 2008
Last Updated
May 10, 2012
Sponsor
Athersys, Inc
Collaborators
PPD, Angiotech Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00677222
Brief Title
Safety Study of AMI MultiStem® to Treat Heart Attacks
Official Title
A Phase I, Multicenter, Dose-Escalation Trial Evaluating the Safety of Allogeneic AMI MultiStem® in Patients With Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Athersys, Inc
Collaborators
PPD, Angiotech Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
Keywords
Acute Myocardial Infarction, Heart Attack
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Treatment arm
Arm Title
2
Arm Type
No Intervention
Arm Description
Registry Arm -standard of care
Intervention Type
Biological
Intervention Name(s)
AMI MultiStem®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of adverse events during the first 24 hours after administration of AMI MultiStem® and post acute adverse events up to 30 days following AMI
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Evaluation of longer term safety and cardiac function over 12 months following AMI
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Penn, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Warren Sherman, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiology PC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Facility Name
The Care Group
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Metro Health
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Hamot Medical Center
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16507
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22052917
Citation
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.
Results Reference
derived
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Safety Study of AMI MultiStem® to Treat Heart Attacks
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