NBS10 (Also Known as AMR-001) Versus Placebo Post ST Segment Elevation Myocardial Infarction (PreSERVE-AMI)

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.

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.

Study Overview

• Status: Completed
• Conditions: ST Segment Elevation Myocardial Infarction
• Intervention / Treatment: Other: placebo; Biological: NBS10

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC (Huntsville Hospital)
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Mercy Gilbert Medical Group
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Arizona
  • California
    • La Jolla, California, United States, 92037
      • Scripps-La Jolla, CA
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine - University of Southern California
    • Oxnard, California, United States, 93030
      • St.Johns Regional Hospital and Medical Center
    • Stanford, California, United States, 94305
      • Standford University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida-Gainesville
    • Orlando, Florida, United States, 32806
      • Orlando Health Medical Center
    • Tampa, Florida, United States, 33513
      • Pepin Heart Institute - Florida Hospital -Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • St. Joseph's Research Institute
    • Atlanta, Georgia, United States, 30322
      • Emory University Medical Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Heart Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Downer's Grove, Illinois, United States, 60515
      • Advocate Health and Hospital Corp.
    • Elmhurst, Illinois, United States, 60126
      • Advocate Health and Hospital Corp.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent's Medical Group/St. Vincent's Heart Center of Indiana
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Gill Heart Institute
    • Louisville, Kentucky, United States, 40207
      • Louisville Cardiology Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Med Center, Baltimore
  • Massachusetts
    • Framingham, Massachusetts, United States, 01702
      • MetroWest Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Systems
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center PC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Cardiology Asociates Research LLC
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Newark, New Jersey, United States, 07103
      • University of Medicine and Dentistry of New Jersey
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center-Brooklyn
    • Buffalo, New York, United States, 14203
      • Buffalo General Medical Center/Roswell Park Cancer Institute
    • Stony Brook, New York, United States, 11794-8167
      • Stony Brook University Hospital and Medical Center
    • Valhalla, New York, United States, 10532
      • Westchester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28024
      • Presbyterian CVI Research
    • Gastonia, North Carolina, United States, 28054
      • CaroMont Heart
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oklahoma
    • Oaklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health and Sciences Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University/Hahnemann University Medical Center
    • Pittsburg, Pennsylvania, United States, 15213
      • University of Pittsburg Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Miriam Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation/Baptist Hospital
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Heart
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch - Galveston
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Texas Heart Institute
    • San Antonio, Texas, United States, 78229
      • Methodist Health Systems of San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • UVA Health System Cardiology Research
    • Lynchburg, Virginia, United States, 25401
      • Centra Lynchburg General Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Health Care Metro, Inc/St. Lukes Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; matching placebo	Other: placebo; matching placebo
Experimental: NBS10; active treatment - CD34+ cells	Biological: NBS10; dosage = 10 or more million CD34+ cells via intracoronary infusion; Other Names: AMR-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine safety and efficacy of intracoronary infusion of NBS10.	The primary endpoint includes the occurrence of AE's, SAE's and Major Adverse Cardiac Events (MACE) and the assessment of myocardial perfusion measured by quantitative gated SPECT MPI specifically looking at resting total severity score.	primary outcome measured at 6 months

Collaborators and Investigators

• Sponsor: Lisata Therapeutics, Inc.
• Investigators: Study Director: Tom Moss, MD, Lisata Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: December 9, 2011
• First Submitted That Met QC Criteria: December 16, 2011
• First Posted (Estimate): December 20, 2011

Study Record Updates

• Last Update Posted (Estimate): April 28, 2016
• Last Update Submitted That Met QC Criteria: April 26, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: STEMI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: 002 (University of CT Health Center)