Clinical trial NCT01495364: NBS10 (Also Known as AMR-001) Versus Placebo Post ST Segment Elevation Myocardial Infarction
Official title: A Prospective Randomized Double Blind Placebo Controlled Phase II Trial of Intra-coronary Infusion of AMR-001, a Bone Marrow Derived Autologous CD34+ Selected Cell Product, in Patients With Acute Myocardial Infarction.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ST Segment Elevation Myocardial Infarction
Keywords: STEMI
Lead sponsor: Lisata Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-20
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and efficacy of intracoronary artery administered autologous bone marrow derived stem cells in subjects post ST segment elevation myocardial infarction (STEMI). This will be assessed by evaluating and comparing the autologous stem cell treatment group to the control group in terms of the occurrence of AE's, SAE's and Major Adverse Cardiac Events (MACE), by the change in myocardial perfusion (RTSS) measured quantitatively by gated single photon emission computed tomography myocardial perfusion imaging (gated SPECT MPI), and other secondary endpoints such as LVEF measured by cardiac MRI in addition to other endpoints.

Detailed description: Efficacy endpoint is at 6 months. Clinical endpoints and safety will be measured through 36 months.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older.
2. Acute ST elevation myocardial infarction meeting ACC/AHA criteria, with symptoms of chest pain within 3 days of admission. Criteria include (ST elevation \> 1mm in limb leads or 2 mm in two or more precordial leads, and increased levels of troponin, CPK MB or both).

   Chest pain syndrome can extend to more than 3 days prior to admission if its course is consistent with transient/intermittent ischemia rather than symptoms that are continuous suggesting ongoing infarction extending beyond 3 days.
3. Successful stent placement and reperfusion within 3 days of chest pain onset and with TIMI Flow score of 2 or 3 and infarct related artery (IRA) with \<20% stenosis after revascularization.
4. Wall motion abnormality associated with the target lesion
5. NYHA heart failure class I, II or III.
6. Study entry LVEF \<48% determined by CMR no sooner than 96 hours from stent placement.
7. Able to provide informed written consent and willing to participate in all required study follow-up assessments.
8. Subjects must have an INR ≤ 2.0 within 2 days of the bone marrow collection.
9. Subjects must have a Hgb ≥ 10 grams/dL, WBC ≥ 3500 cells/mm3, a platelet count ≥ 100,000 cells/mm3, serum creatinine ≤ 2.5, and total bilirubin ≤ 2.0 within 7 days of the bone marrow collection or by end of screening phase.
10. Expected survival of at least one year.
11. Females of child bearing potential agree to use birth control (barrier method accepted) for one month post bone marrow harvest.

EXCLUSION CRITERIA

1. Continuous/ongoing chest pain - unremitting and unresponsive to nitroglycerin or rest - persisting 4 or more days before stent placement. If the chest pain syndrome is transient and/or intermittent - even if it began more than 3 days prior to admission - the patient is not excluded.
2. Subjects in cardiogenic shock (systolic pressure \< 80mm/Hg, on vasopressors, or intra-aortic counterpulsation) at the time of consenting. Subjects who recover from cardiogenic shock by the time of consenting are eligible.
3. Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine, prasugrel, etc).
4. Subjects receiving warfarin who have an INR \>2 or with major bleeding requiring active transfusion support.
5. Subjects who require continuous anticoagulation during the time when the bone marrow harvest is scheduled, as heparin must be discontinued for 4 hours prior to and 24 hours after bone marrow harvest procedure. (See Appendix VII.)
6. Subjects with severe cardiac valvular disease expected to undergo surgery within 1 year.
7. Subjects with known severe immunodeficiency states (AIDS).
8. Cirrhosis requiring active medical management.
9. Malignancy requiring active treatment (except basal cell skin cancer).
10. Subjects with documented active alcohol and /or other substance abuse.
11. Females of child bearing potential unless a pregnancy test is negative within 7 days of the mini-bone marrow harvest.
12. Re-occlusion of the IRA prior to the infusion procedure.
13. Planned revascularization intervention during the next 6 months (A second PCI can be performed if done prior to qualifying CMR at least 96 hours post primary PCI).
14. Participation in an ongoing investigational trial.
15. Active or suspected bacterial infection requiring systemic intravenous antibiotics.

Primary outcomes:
measure: To determine safety and efficacy of intracoronary infusion of NBS10.
timeFrame: primary outcome measured at 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research, LLC (Huntsville Hospital)
state: Alabama
city: Gilbert
country: United States
facility: Mercy Gilbert Medical Group
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: La Jolla
country: United States
facility: Scripps-La Jolla, CA
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine - University of Southern California
state: California
city: Oxnard
country: United States
facility: St.Johns Regional Hospital and Medical Center
state: California
city: Stanford
country: United States
facility: Standford University School of Medicine
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida-Gainesville
state: Florida
city: Orlando
country: United States
facility: Orlando Health Medical Center
state: Florida
city: Tampa
country: United States
facility: Pepin Heart Institute - Florida Hospital -Tampa
state: Florida
city: Atlanta
country: United States
facility: Emory University Medical Center
state: Georgia
city: Atlanta
country: United States
facility: St. Joseph's Research Institute
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Heart Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Downer's Grove
country: United States
facility: Advocate Health and Hospital Corp.
state: Illinois
city: Elmhurst
country: United States
facility: Advocate Health and Hospital Corp.
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent's Medical Group/St. Vincent's Heart Center of Indiana
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Gill Heart Institute
state: Kentucky
city: Louisville
country: United States
facility: Louisville Cardiology Medical Group
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Med Center, Baltimore
state: Maryland
city: Framingham
country: United States
facility: Metrowest Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Detroit Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center PC
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Tupelo
country: United States
facility: Cardiology Asociates Research LLC
state: Mississippi
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Brooklyn
country: United States
facility: Maimonides Medical Center-Brooklyn
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center/Roswell Park Cancer Institute
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital and Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian CVI Research
state: North Carolina
city: Gastonia
country: United States
facility: CaroMont Heart
state: North Carolina
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oaklahoma City
country: United States
facility: University of Oklahoma Health and Sciences Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University/Hahnemann University Medical Center
state: Pennsylvania
city: Pittsburg
country: United States
facility: University of PIttsburg Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Memphis
country: United States
facility: Stern Cardiovascular Foundation/Baptist Hospital
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch - Galveston
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: Methodist Health Systems of San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Charlottesville
country: United States
facility: UVA Health System Cardiology Research
state: Virginia
city: Lynchburg
country: United States
facility: Centra Lynchburg General Hospital
state: Virginia
city: Milwaukee
country: United States
facility: Aurora Health Care Metro, Inc/St. Lukes Medical Center
state: Wisconsin
Study officials:
affiliation: Lisata Therapeutics, Inc.
name: Tom Moss, MD
role: STUDY_DIRECTOR
affiliation: Emory University
name: Arshed Quyyumi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quyyumi AA, Vasquez A, Kereiakes DJ, Klapholz M, Schaer GL, Abdel-Latif A, Frohwein S, Henry TD, Schatz RA, Dib N, Toma C, Davidson CJ, Barsness GW, Shavelle DM, Cohen M, Poole J, Moss T, Hyde P, Kanakaraj AM, Druker V, Chung A, Junge C, Preti RA, Smith RL, Mazzo DJ, Pecora A, Losordo DW. PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI. Circ Res. 2017 Jan 20;120(2):324-331. doi: 10.1161/CIRCRESAHA.115.308165. Epub 2016 Nov 7.