Safety Study of AMI MultiStem® to Treat Heart Attacks

This study has been completed.
Sponsor:
Collaborators:
PPD
Angiotech Pharmaceuticals
Information provided by (Responsible Party):
Athersys, Inc
ClinicalTrials.gov Identifier:
NCT00677222
First received: May 12, 2008
Last updated: May 10, 2012
Last verified: May 2012

May 12, 2008
May 10, 2012
May 2008
March 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00677222 on ClinicalTrials.gov Archive Site
Evaluation of longer term safety and cardiac function over 12 months following AMI [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Safety Study of AMI MultiStem® to Treat Heart Attacks
A Phase I, Multicenter, Dose-Escalation Trial Evaluating the Safety of Allogeneic AMI MultiStem® in Patients With Acute Myocardial Infarction

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myocardial Infarction
Biological: 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.
  • Experimental: 1
    Treatment arm
    Intervention: Biological: AMI MultiStem®
  • No Intervention: 2
    Registry Arm -standard of care
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. Epub 2011 Nov 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
February 2012
March 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00677222
AMI-07-001
Yes
Athersys, Inc
Athersys, Inc
  • PPD
  • Angiotech Pharmaceuticals
Principal Investigator: Marc Penn, MD The Cleveland Clinic
Principal Investigator: Warren Sherman, MD Columbia University
Athersys, Inc
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP