Please select the eligibility criteria that correspond to the clinical trial below.
Title: A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.


Options:
A: Inclusion Criteria:

* Subjects with functional class (CCS) III or IV angina.
* Subjects who have attempted "best" medical therapy without control of symptoms.
* All subjects must have a recent coronary angiogram (within the last 3 months).
* Clinical signs and symptoms of clinically significant ischemia on nuclear perfusion imaging.
* Subjects must be able to complete a minimum of 1 minute but no more than 6 minutes of the Standard Bruce Protocol.
* Subject experiences angina during the baseline exercise tolerance test.
* Subjects must either be no longer capable of reproduction or taking acceptable measures to prevent reproduction during the study.
* Normal renal function.
* Normal liver function.
* Normal blood count.

Angiographic Inclusions:

* Total occlusion of an epicardial coronary artery.
* Candidates at high risk for percutaneous coronary angioplasty of treatment zone(s) based upon clinical or anatomic considerations including but not limited to the following: diabetes, congestive heart failure (severe right heart failure, NYHA class III or IV), left main disease, pulmonary hypertension, severe proximal vessel tortuosity, severe bendpoint obstructions, diffuse disease (\>2 cm in length), small vessel (\<2 mm reference diameter), stenosis which are either diffuse (\>2 cm in length) or distal, incessant restenosis lesions, unfavorable bifurcation stenosis, and degenerated or thrombosed saphenous vein grafts.

Exclusion Criteria:

* Predominant congestive heart failure symptoms.
* Patients who have been hospitalized with a primary diagnosis of CHF in the prior 6 months.
* Patients who have had diuretics added to their medical regimen or an increase in diuretic dosage for signs or symptoms of CHF in the past 6 months.
* Patients with a left ventricular ejection fraction of less than 25% as determined by transthoracic echocardiography.
* Patients with physical findings consistent with ongoing uncontrolled CHF.
* Myocardial infarction within 30 days of treatment.
* Successful coronary revascularization procedures within 3 months of study enrollment.
* Documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment.
* History of severe aortic stenosis or insufficiency; severe mitral stenosis; or severe mitral insufficiency.
* Severe co-morbidity associated with a reduction in life expectancy of less than 1 year.
* Subjects with PT, PTT or platelet counts greater than the upper limit of normal and those with a hematocrit \<35%.
* Subjects with uncontrolled hypertension.
* Currently enrolled in another investigational device or drug trial (IDE or IND) that has not completed the required follow-up period.
* History of alcohol or drug abuse within 3 months of screening.
* Joint or peripheral vascular disease that severely limits treadmill walking.
* Chronic obstructive pulmonary disease that severely limits walking or FEV1.0\<30% predicted.
* Subjects who are pregnant or lactating.
* Males and females who are capable of reproduction and will not take acceptable measures to prevent reproduction during the study.
* Subjects who test positive for HIV, hepatitis B or hepatitis C, have a chronic inflammatory disease, autoimmune disease or are on chronic immunosuppressive medications.
* Subjects with a known hypersensitivity to E. coli-derived proteins.
* Subjects with evidence (clinical, laboratory, or imaging) of cancer recurrence within the past 5 years (other than non-melanoma skin cancer or in situ cervical carcinoma).
B: Inclusion Criteria:

* LVEF less than 45%
* Functional class III or IV angina
* At least 7% reversibility by Single Photon Emission Computed Tomography (SPECT) nuclear study
* there are additional inc. criteria

Exclusion Criteria:

* AGe \<18 or \>70 years of age
* Constant atrial fibrillation
* Left ventricular (LV) thrombus
* History of malignancy in the last 5 years
* LV wall thickness of \< 8 mm at the target site
* there are additional exclusion criteria
C: Inclusion Criteria:

* Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory angina
* subjects without control of their angina symptoms, in spite of maximal tolerated doses of anti-anginal drugs, must be on optimal therapy for their angina and on a stable anti-anginal medication regimen for at least 1 month prior to entering the screening period of the study
* identified as unsuitable for conventional revascularization
* recent coronary angiogram (within the last 12 months) to document the coronary anatomy and to verify the revascularization procedures
* subjects must have objective evidence of inducible ischemia or viable myocardium in the potential target injection zone
* a left ventricular ejection fraction equal to or greater than 25% by ECHO or single photon emission computed tomography (SPECT) at screening
* subjects must experience at minimum an average of 7 angina or anginal equivalent episodes per week
* subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes on a treadmill following the Modified Bruce Protocol
* subjects must experience angina or anginal equivalent episodes during the screening exercise treadmill test
* female subjects must either be no longer capable of reproduction or using medically valid contraception to prevent pregnancy during the study
* subjects must be willing and able to comply with specified follow-up evaluations

Exclusion Criteria:

* predominant congestive heart failure
* myocardial infarction within 60 days of treatment
* successful or partially successful coronary revascularization procedures (any vessel) within 6 months of study enrollment
* placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure in the past 90 days
* documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment
* history of moderate to severe aortic stenosis or severe aortic insufficiency; severe mitral stenosis or severe mitral insufficiency
* prosthetic aortic valve replacement
* evidence of any life-threatening arrhythmia that requires intervention on the 24-hour Holter monitor. Life-threatening arrhythmia that is successfully treated with an implantable cardioverter defibrillator (ICD) is not exclusionary.
* splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive pulmonary disease, renal failure or cancer \[exceptions: in-situ skin cancer or fully removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5 years with no history of a stem cell transplant\])
* sickle cell disease or sickle cell trait
* platelet count greater than 10% above the upper limit of normal or a platelet count below 100,000 if on Clopidogrel or 50,000 without Clopidogrel
* hematocrit \<30%
* serum creatinine \>2.5 mg/dL
* any clinically significant laboratory abnormality on screening laboratories
* currently enrolled in another IDE or IND that has not completed the protocol required primary follow-up period (excludes 15 year follow up of gene therapy trials)
* history of alcohol or drug abuse within 3 months of screening
* joint or peripheral vascular disease or neurologic disease that severely limits treadmill walking
* chronic obstructive pulmonary disease that severely limits walking or FEV1 \<30% predicted
* females who are pregnant or lactating
* female subjects who are capable of reproduction and will not use medically valid contraception to prevent pregnancy during the study
* subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic immunosuppressive medications or have had a prior stem cell transplant
* subjects with a known hypersensitivity to E. coli-derived proteins, or to any component of Neupogen (Filgrastim) or G-CSF
* subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject´s ability to provide informed consent and/or comply with protocol procedures
D: 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.

Answer: C