Clinical trial NCT01508910: Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Myocardial Ischemia
Refractory Angina Pectoris
Advanced Coronary Heart Disease
Lead sponsor: Lisata Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-12
Enrollment: 291
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Total Exercise Time on Exercise Tolerance Test (ETT) Using the Modified Bruce Protocol
timeFrame: Baseline and 12 month visit
Secondary outcomes:
measure: Angina Frequency (Episodes Per Week) at the 12 Month Follow-up Visit
timeFrame: Baseline and 12 month visit
measure: Change From Baseline in Total Exercise Time on Exercise Tolerance Test (ETT) at the 6 Month Follow-up Visit
timeFrame: Baseline and 6 month visit
measure: Angina Frequency (Episodes Per Week) at the 6 Month Follow-up Visit
timeFrame: 6 month visit
measure: Percentage of Participants With Incidences of MACE From Randomization Until the End of the 24 Month Follow-up Period
timeFrame: From randomization until the end of the 24 month follow-up period
measure: Percentage of Participants With at Least One Serious Adverse Event (SAE) From Randomization Until the End of the 24 Month Follow-up Period
timeFrame: From randomization until the end of the 24 month follow-up period
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Gilbert
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oxnard
country: United States
state: California
city: San Diego
country: United States
state: California
city: Stanford
country: United States
state: California
city: Boynton Beach
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Saginaw
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Haddon Heights
country: United States
state: New Jersey
city: Newark
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Germantown
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
Study officials:
affiliation: Caladrius Biosciences
name: Caladrius Study Director
role: STUDY_DIRECTOR
References:
citation: Povsic TJ, Henry TD, Traverse JH, Fortuin FD, Schaer GL, Kereiakes DJ, Schatz RA, Zeiher AM, White CJ, Stewart DJ, Jolicoeur EM, Bass T, Henderson DA, Dignacco P, Gu Z, Al-Khalidi HR, Junge C, Nada A, Hunt AS, Losordo DW; RENEW Investigators. The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina. JACC Cardiovasc Interv. 2016 Aug 8;9(15):1576-85. doi: 10.1016/j.jcin.2016.05.003.
citation: Povsic TJ, Junge C, Nada A, Schatz RA, Harrington RA, Davidson CJ, Fortuin FD, Kereiakes DJ, Mendelsohn FO, Sherman W, Schaer GL, White CJ, Stewart D, Story K, Losordo DW, Henry TD. A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study. Am Heart J. 2013 Jun;165(6):854-861.e2. doi: 10.1016/j.ahj.2013.03.003. Epub 2013 Apr 19.