Safety & Efficacy of Adipose-Derived Regenerative Cells in the Treatment of Chronic Myocardial Ischemia (ATHENA II) (ATHENA II)

Adipose-derived Regenerative Cells in the Treatment of Patients With Chronic Ischemic Heart Disease Not Amenable to Surgical or Interventional Revascularization II

This is a prospective, randomized, placebo-controlled, double blind safety and efficacy clinical trial.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia
• Intervention / Treatment: Device: Celution System; Device: Placebo

Detailed Description

To assess the safety and efficacy of Adipose-Derived Regenerative Cells (ADRCs) delivered via an intramyocardial route in the treatment of chronic ischemic heart disease in patients who are not eligible for percutaneous or surgical revascularization.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 11100
      • University Hospital Case Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females > 20 and < 80 years of age
2. Significant multi-vessel coronary artery disease not amenable to percutaneous or surgical revascularization
3. CCS Angina Functional Class II-IV and/or NYHA Stages of Heart Failure Class II or III
4. On maximal medical therapy for anginal symptoms and/or heart failure symptoms
5. Hemodynamic stability (SBP ≥ 90 mm/Hg, HR <110)
6. Ejection fraction ≥ 20% and ≤ 45%
7. Inducible ischemia using an objective assessment of ischemia within 1 year of screening (i.e. exercise ECG changes, SPECT)
8. Left ventricular wall thickness ≥ 8 mm at the target site for cell injection

Exclusion Criteria:

1. Atrial fibrillation or flutter without a pace maker that guarantees a stable heart rate
2. Unstable angina
3. LV thrombus, as documented by echocardiography
4. Planned staged treatment of CAD or other intervention on the heart
5. Platelet count < 100,000/mm3
6. WBC < 2,000/mm3
7. TIA or stroke within 90 days prior to randomization
8. ICD shock within 30 days prior to randomization
9. Any condition requiring immunosuppressive medication
10. A high-risk acute coronary syndrome (ACS) or a myocardial infarction in the 60 days prior to randomization
11. Revascularization within 60 days prior to randomization
12. Inability to walk on a treadmill except for class IV angina patients who will be evaluated separately
13. Hepatic dysfunction, as defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (x ULN)
14. Hemoglobin ≤ 10.0 g/dL

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
Experimental: ADRCs; Adipose-Derived Regenerative Cells (ADRCs) processed by the Celution System: 0.8 x 10^6 cells/kg body weight (not to exceed 80.0 x 10^6 cells); Delivered via the MYOSTAR™ Injection Catheter in 15 intramyocardial injections	Device: Celution System; ADRCs processed by the Celution System for reintroduction into the myocardium
Placebo Comparator: Placebo; Placebo - Physiological Solution; Inactive substance (Lactated Ringers + autologous blood); Delivered via the MYOSTAR™ Injection Catheter in 15 intramyocardial injections	Device: Placebo; Physiological solution made of Lactated Ringers solution and a small amount (<1mL) of autologous blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy - Change in Minnesota Living with Heart Failure Questionnaire	Change in Minnesota Living with Heart Failure Questionnaire prior to treatment and at 6 months post treatment.	6 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy - Change in mVO2	Change in mVO2 at 6 months as assessed by Exercise Tolerance Test	6 months post treatment
Secondary Efficacy - Change in LVESV/LVEDV	Change in LVESV/LVEDV at 6 months as assessed by Echocardiography	6 months post treatment
Secondary Efficacy - Change in Ejection Fraction	Change in Ejection Fraction (%) at 6 months assessed by 2D Contrast Echocardiography	6 months post treatment
Secondary Efficacy - Change in perfusion defect	Change in perfusion defect at 6 months assessed by Rest/Pharmacologic Stress SPECT	6 months post treatment
Secondary Efficacy - Resource Utilization	Resource utilization - hospital length of stay, re-hospitalization for cardiac related events	through 12 months post treatment
Secondary Efficacy - Change in heart failure symptoms, angina, and quality of life	Change in heart failure symptoms, angina, and quality of life assessed by - NYHA classification, CCS classification, MLHFQ (other than 6 months)	through 12 months post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Number of Patients Experiencing Treatment Emergent SAEs		Treatment through 12 months
Safety - Number of Patients Experiencing Arrhythmias Assessed via Holter monitor		Screening through 3 months post treatment
Safety - Number of patients that experience a MACE	Number of patients that experience a Major Adverse Cardiac Event (MACE)	Treatment through 12 months

Collaborators and Investigators

• Sponsor: Cytori Therapeutics
• Investigators: Principal Investigator: Emerson C. Perin, MD, PhD, The Stem Cell Center at Texas Heart Institute; Principal Investigator: Timothy Henry, MD, Cedars-Sinai Medical Center

Publications and helpful links

General Publications

• Henry TD, Pepine CJ, Lambert CR, Traverse JH, Schatz R, Costa M, Povsic TJ, David Anderson R, Willerson JT, Kesten S, Perin EC. The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction. Catheter Cardiovasc Interv. 2017 Feb 1;89(2):169-177. doi: 10.1002/ccd.26601. Epub 2016 Sep 23.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: January 30, 2014
• First Posted (Estimate): February 3, 2014

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Coronary artery disease; Chronic Heart Failure; adult stem cells; Ischemic heart disease; adipose derived regenerative cells
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: ATHENA II