Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina (RENEW)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01508910
First received: January 10, 2012
Last updated: December 22, 2013
Last verified: December 2013
  Purpose

The purpose of the study is to assess the safety and efficacy of targeted intramyocardial delivery of Auto-CD34+ cells for increasing exercise time and amelioration of anginal symptoms in subjects with refractory angina and chronic myocardial ischemia.


Condition Intervention Phase
Chronic Myocardial Ischemia
Refractory Angina Pectoris
(Advanced) Coronary Heart Disease
Biological: Auto-CD34+ cells
Biological: Placebo: Diluent used to suspend Auto-CD34+ cells
Other: Standard of care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-blinded, Active-control and Unblinded Standard of Care (SOC) Controlled Study to Determine the Efficacy and Safety of Targeted Intramyocardial Delivery of Autologous CD34+ Cells (Auto-CD34+ Cells) for Increasing Exercise Capacity During Standardized Exercise Testing in Subjects With Refractory Angina Pectoris and Chronic Myocardial Ischemia

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Change from baseline in total exercise time on exercise tolerance test (ETT) using the Modified Bruce Protocol [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Angina frequency (episodes per week) [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Subjects will self-report angina episodes utilizing an electronic diary for 4 weeks at baseline and before the 3, 6 and 12 month follow-up visit.

  • Change from baseline in total exercise time on ETT at the 6 month follow-up timepoint [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
  • Angina frequency (episodes per week) at the 6 month follow-up timepoint [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Incidence of major adverse cardiac events and other serious adverse events in all subjects [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 291
Study Start Date: April 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Targeted intramyocardial delivery of 1 x 10^5 Auto-CD34+ cells after granulocyte-colony stimulating factor (G-CSF) mobilization and apheresis
Biological: Auto-CD34+ cells
10 intramyocardial injections of 0.2 mL per injection site of Auto-CD34+ cells
Placebo Comparator: Active Control Arm
Targeted intramyocardial delivery of placebo after G-CSF mobilization and apheresis
Biological: Placebo: Diluent used to suspend Auto-CD34+ cells
10 intramyocardial injections of 0.2 mL per injection site of placebo
Unblinded Standard of Care (SOC) Arm
No study-related procedures will be performed.
Other: Standard of care
Standard of care for refractory angina

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Male or female participants who are 21 to 80 years of age at the time of signing the informed consent.
  • Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic refractory angina.
  • Participants without control of their angina symptoms in spite of maximal tolerated doses of anti-angina drugs. Participants must be on optimal therapy for their angina and must have been on a stable anti-anginal medication regimen for at least 4 weeks before signing the informed consent form.
  • Participants with obstructive coronary disease unsuitable for conventional revascularization due to unsuitable anatomy or comorbidity as determined at the site and confirmed by an independent adjudication committee.
  • Participants must have evidence of inducible myocardial ischemia.
  • Participants must experience angina episodes.
  • Participants must be able to complete 2 exercise tolerance tests on the treadmill within 3 weeks of randomization.
  • If female of childbearing potential, subject must not be pregnant and agree to employ adequate birth control measures for the duration of the study.

Main Exclusion Criteria:

  • Cardiovascular hospitalization within 60 days prior to potential study enrollment. Participant has had a successful or partially successful coronary artery bypass graft (CABG) within 6 months or PCTA within 60 days of potential study enrollment.
  • Participant has had a placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure within 180 days of potential study enrollment.
  • Participant has documented stroke or transient ischemic attacks (TIAs) within 60 days of potential study enrollment.
  • Participant has a history of moderate to severe aortic stenosis; or severe aortic insufficiency; or severe mitral stenosis; or severe mitral insufficiency.
  • Participant has a prosthetic aortic valve or a mechanical mitral valve replacement.
  • Participant has severe co-morbidity associated with a reduction in life expectancy to less than 3 years as a result of chronic medical illnesses.
  • Participants with cancer are excluded with the following exceptions:

    • Subjects with in-situ non-melanoma skin cancer or in-situ cervical cancer are not excluded.
    • Participants that have been cancer free for >= 5 years as determined by their oncologist are not excluded. Subjects with a prior history of stem cell transplant for cancer are excluded no matter how long they have been cancer-free.
  • Participants with a history of leukemia or other bone marrow disease.
  • Participant has sickle cell disease or sickle cell trait.
  • Participants with proliferative retinopathy.
  • Participants with Hb A1c > 9%.
  • Participant has platelet counts >10% above the upper limit of normal (ULN) or platelet counts < 70,000.
  • Participant has a hematocrit < 30% prior to potential study enrollment.
  • Participant has a serum creatinine > 2.5 mg/dL prior to potential study enrollment.
  • Participant tests positive for HIV, hepatitis B, or hepatitis C, or is on chronic immunosuppressive medications, or has had a previous stem cell transplant.
  • Participant has a known contraindication to Neupogen (filgrastim) or G-CSF.
  • Participant was previously enrolled in an active treatment group of cell therapy trials for cardiovascular disease including any phase of CD34+ stem cell trials.
  • Left ventricular (LV) thickness of < 7 mm in the target areas of injection as measured by during a 2-D echocardiogram (ECHO).
  • Atrial fibrillation, atrial flutter, or other uncontrolled arrhythmias that would prohibit accurate electromechanical mapping and NOGA-guided intramyocardial injection.
  • Bleeding diathesis with an INR > 1.8 when not receiving anti-thrombotic therapy.
  • Hepatic dysfunction as evidenced by elevated AST or ALT levels > 2.5 x ULN.
  • Any previous transplant requiring immunosuppression.
  • Disease state requiring chronic immunosuppression.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01508910

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
Gilbert, Arizona, United States
Phoenix, Arizona, United States
United States, California
La Jolla, California, United States
Los Angeles, California, United States
Oxnard, California, United States
San Diego, California, United States
Stanford, California, United States
United States, Florida
Boynton Beach, Florida, United States
Daytona Beach, Florida, United States
Gainesville, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
Tampa, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Augusta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Saginaw, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
Rochester, Minnesota, United States
United States, New Jersey
Haddon Heights, New Jersey, United States
Newark, New Jersey, United States
United States, New York
New York, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
Durham, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
United States, Tennessee
Germantown, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Washington
Seattle, Washington, United States
United States, Wisconsin
Madison, Wisconsin, United States
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Adel Nada, MD, MS Baxter Healthcare Corporation
  More Information

No publications provided by Baxter Healthcare Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01508910     History of Changes
Other Study ID Numbers: 901001, RENEW Study
Study First Received: January 10, 2012
Last Updated: December 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Angina Pectoris
Myocardial Ischemia
Coronary Artery Disease
Coronary Disease
Heart Diseases
Ischemia
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014