Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Controlled Clinical Trial of the Use of Autologous Bone Marrow Derived Progenitor Cells to Salvage Myocardium in Patients With Acute Anterior Myocardial Infarction
Brief Summary: Study hypothesis :

The purpose of this study is to determine whether Intracoronary infusion of autologous bone marrow derived progenitor cells to patients undergoing primary angioplasty for acute anterior myocardial infarction will lead to an improvement in cardiac function greater than that seen by placebo alone.

Aims

* To demonstrate that it is safe and feasible to deliver autologous bone marrow derived stem cells within hours of the primary angioplasty procedure
* To demonstrate the effects of autologous bone marrow derived stem cells on cardiac function using cardiac MRI (or cardiac CT), echocardiography and left ventriculography.
* To demonstrate the effect of autologous bone marrow derived stem cells in addition to standard care leads to improvement in cardiac function compared to patients saline(placebo) and standard care.


Options:
A: Inclusion Criteria:

* Diagnosis of ischemic or non-ischemic dilated cardiomyopathy according to WHO criteria. Ischemic: DCM in a patient with a history of myocardial infarction or evidence of clinically significant (\>/= 70% narrowing of a major epicardial artery) coronary artery disease. Non-ischemic: Dilation and impaired contraction of left ventricle or both ventricles of idiopathic, familial/genetic, viral and/or immune, toxic origin, or associated with recognized cardiovascular disease in which the degree of myocardial dysfunction is not explained by normal loading conditions or the extent of ischemic damage.
* No other cardiac surgery or percutaneous cardiac interventions likely to produce clinical improvement, as determined by an interventional cardiologist (for PTCA) and a cardiothoracic surgeon (for CABG). This condition is satisfied in patients w/chronic ischemic disease who have previously been successfully revascularized but have failed to show clinical improvement. All patients who are candidates for revascularization are ineligible for participation.
* LVEF \</= 30% by echocardiogram within 30 days prior to randomization.
* Symptomatic heart failure in NYHA class III or IV.
* Able to comply with scheduled visits in cardiac out-patient clinic.
* Able to tolerate study procedures, including bone marrow aspiration, cardiac CT, metabolic stress test,6 minute walk test.
* Males and females, 18-86 years of age.
* Life expectancy of 6 months or more in the opinion of the investigator.
* Able to give informed consent.
* Normal organ and marrow function (Leukocytes \>/= 3,000/microgram, Absolute neutrophil count \>/= 1,500/microgram, Platelets \>/= 140,000/microgram, AST(SGOT)/ALT (SGPT) \</= 2.5 X institutional standards range and Creatinine \</= 2.5 mg/dL).
* Controlled blood pressure (systolic blood pressure \</= 140; diastolic blood pressure \</= 90 mmHg) and established anti-hypertensive therapy as necessary prior to entry into the study.
* Stable, standard medical therapy for DCM for at least 1 month with NO new medications to treat the disease introduced in the last 3 months. Standard medical therapy includes: Placement of AICD unless contraindicated (refusal of AICD not considered valid contraindication), use of ACE inhibitors and/or AT-1 receptor blockers as well as loop diuretics unless contraindicated and, depending on the type of heart failure associated with the disease, standard therapy may also include use of vasodilators, beta blockers, digoxin, and aldosterone or other medications.
* Pre-existing conditions are adequately controlled in the opinion of the investigator.
* Fertile patients must agree to use an appropriate form of contraception while participating in the study.

Exclusion Criteria:

* Severe primary valvular heart disease including, but not limited to, aortic valve stenosis and insufficiency.
* Known history of COPD defined as Gold stage IIB (FEV1/FVC\<70% with 30%\</=FEV1\<50% predicted, with or without chronic symptoms of cough, sputum production, dyspnea) or more severe or restrictive pulmonary disease.
* Known history of primary pulmonary hypertension.
* VAD implantation.
* Myocardial infarction within 4 weeks prior to randomization.
* History of life-threatening ventricular arrhythmia, except if an AICD is implanted.
* Unstable angina, characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration.
* Patients at high risk for complications due to injection procedure (e.g. patients who have severe peripheral atherosclerotic disease that does not allow advancement of the catheter; patients who have a prosthetic aortic or mitral valve; patients who have a LV thrombus or aneurysm; patients who have an aortic dissection or aneurysm, etc.).
* Patients w/poorly controlled diabetes mellitus (HbAlc\>9.0%).
* Patients receiving treatment with hematopoietic growth factors (e.g. EPO, G-CSF).
* Patients who require uninterruptible anticoagulation therapy (e.g. warfarin)that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections; OR patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration and transendocardial injections, unless contraindicated.
* Known cancer and undergoing treatment including chemotherapy and radiation.
* Patients requiring continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 1 month before aspiration or 6 months after injection procedure.
* End stage renal disease requiring dialysis.
* Patients pregnant or lactating; positive for hCG
* History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1 drink = 5 oz of wine or 12 oz \[360mL\] of beer or 1.5 oz \[45mL\]) of hard liquor or history of illicit drug use w/in 6 months of screening.
* Known allergies to protein products (horse or bovine serum, or porcine trypsin) used in the ex-vivo cell production process.
* BMI of 40 Kg/m2 or greater.
* Patients receiving experimental medications or participating in another clinical study within 30 days of screening.
* HIV or syphilis, positive at time of screening.
* Active Hepatitis B or Hepatitis C infection at the time of screening.
* Patient determined unsuitable for cellular therapy, in the opinion of the investigator or sponsor.
* Patients receiving anti-angiogenic drugs (e.g. anti-VEGF).
* Known allergy or sensitivity to contrast agents used in imaging procedures.
* Minimum LV wall thickness of less than 6mm as determined by ECHO.
B: Inclusion Criteria:

* Patients presenting to the Heart Attack Centre with acute anterior myocardial infarction (ST elevation in at least 2 contiguous anterior leads ≥ 0.2 mV) and treated with acute PCI with stent implantation within 24 hours after symptom onset
* Acute PCI / stent implantation has been successful (residual stenosis visually \< 30% and TIMI flow ≥ 2).
* At the time of inclusion patient no longer requires i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump)
* Significant regional wall motion abnormality in LV angiogram at the time of acute PCI in the LAD territory
* Age 18 - 80 Years (primary angioplasty confers an adverse prognosis in those over the age of 80 years)
* Written informed consent in the recruiting centres native language

Exclusion Criteria:

* Regional wall motion abnormality outside the area involved in the index acute myocardial infarction
* Need to revascularise additional vessels, outside the infarct artery as a planned procedure (these vessels can be treated at baseline)
* Arteriovenous malformations or aneurysms
* Active infection, or fever or diarrhoea within last 4 weeks
* Chronic inflammatory disease
* Known HIV infection or active hepatitis
* Neoplastic disease without documented remission within the past 5 years
* Cerebrovascular insult within 3 months
* Impaired renal function (creatinine \> 200mmol) at the time of cell therapy
* Significant liver disease (GOT \> 2x upper limit) or spontaneous INR \> 1,5)
* Anemia (hemoglobin \< 8.5 mg/dl)
* Platelet count \< 100.000/µl
* Hypersplenism
* Known allergy or intolerance to clopidogrel, heparin or abciximab
* History of bleeding disorder
* Gastrointestinal bleeding within 3 months
* Major surgical procedure or trauma within 2 months
* Uncontrolled hypertension
* Pregnancy
* Mental retardation leading to inability to obtain informed consent
* Previously performed stem / progenitor cell therapy
* Participation in another clinical trial within the last 30 days
C: Inclusion Criteria:

1. Males and females ≥18 years of age
2. LVEF ≤35% on echocardiogram within 12 months of randomization to undergo MRI
3. Screening cardiac MRI at baseline with:

   Ejection fraction ≤40% No significant hyper enhancement on MRI scan in the opinion of the central imaging lab reviewer
4. Patients with non-ischemic heart failure etiology, as documented by absent or non-obstructive coronary artery disease on x-ray angiography or coronary computed tomography
5. Patients with history of heart failure and treated for at least three months with GDMT
6. NYHA class II-III symptoms
7. Ability to understand and provide signed informed consent
8. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits

Exclusion Criteria:

1. Pregnant or nursing women or those of childbearing age and not using an effective method of contraception
2. History of stroke within 3 months
3. Cardiac surgery within 3 months prior to randomization or the likelihood of a requirement for such procedures during the study period
4. Current ICD or CRT or implantation planned within 6 months of infusion
5. Presence of clinically significant, uncorrected valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, or uncontrolled hypertension
6. History of cardiac arrest or life-threatening arrhythmias within 3 months
7. Treatment with parenteral inotropic agents within 1 month of randomization
8. Anticipated cardiac transplantation within 1 year
9. Illness other than heart failure with life expectancy less than 1 year
10. Received an experimental drug or device within 30 days of randomization
11. Left ventricular assist device or implantation planned in the next 6 months
12. Patients with complex congenital heart disease
13. Uncontrolled seizure disorder
14. Presence of immune deficiency
15. Clinically significant hematologic, hepatic, or renal impairment as determined by screening clinical laboratory tests:

    * Liver disease = ALT or AST \> 3x normal, alkaline phosphatase or bilirubin \>2x normal)
    * Renal disease = estimated glomerular filtration rate as assessed by the MDRD formula \<30 ml/min
    * Hematologic = Unexplained leukocytosis \>10 or hemoglobin \< 9gm/dl
16. Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the investigator or sponsor for which participation in the study would pose a safety risk to the subject
17. Inability to comply with the conditions of the protocol
18. Malignancy within the previous five years, except adequately treated basal cell carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in situ of the cervix
19. Active myocarditis or early postpartum cardiomyopathy (within six months).
20. Systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment
21. Porphyria
22. Allergy to sodium citrate or any "caine" type of local anesthetic
23. Any contraindication for gadolinium use for MRI
24. Patient scheduled for hospice care
25. Clinically relevant abnormal findings in the clinical history, physical examination, ECG, or laboratory tests at the screening assessment that would interfere with the objectives of the study or would preclude safe completion of the study. Abnormal findings could include: known HIV infection or other immunodeficiency state, chronic active viral infection (such as hepatitis B or C), acute systemic infections (defined as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding, or any severe or acute concomitant illness or injury
26. Any other medical, social, or geographical factor that would make it unlikely that the patient could comply with study procedures (e.g., alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location, or noncompliance)
D: Inclusion Criteria:

* Subject is ≥ 18 and \< 75 years old;
* Subject has Heart Failure, New York Heart Association (NYHA) class II or class III with LVEF \> 15% and ≤ 40% as assessed by transthoracic echocardiography;
* Subject has ischemic heart disease;
* Subject has an identifiable (by transthoracic echocardiography) area of transmural scar within the left ventricle;
* Subject is on optimal and stable medical therapy for more than 2 months;
* Subject is willing and able to undergo an ICD implantation, prior to receiving C-Cure™ or already has an ICD implanted;
* Subject agrees to comply with all follow-up evaluations;
* Subject has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent.

Exclusion Criteria:

* Subject has been treated with cell-based therapy;
* Subject has myocardial revascularization by PCI or CABG within 2 months prior to enrolment;
* Subject has had an MI within 2 months prior to enrolment;
* Subject is planned for PCI, CABG or any cardiac surgery;
* Subject has received a biventricular pacemaker within 6 month prior to enrolment;
* Subject has moderate to severe aortic valve heart disease, aortic or mitral prosthetic valve;
* Subject has a significant mitral valve insufficiency (Effective Regurgitant Orifice (ERO) \> 0.2 cm²) with possibility of mitral valve surgery;
* Subject has left ventricular thrombus;
* Subject has LV aneurysma or is a candidate for surgical aneurysmectomy;
* Subject LV ventricular wall thickness is \< 5 mm in the target territory;
* Subject has proven high grade atrioventricular block or sustained ventricular tachyarrhythmias;
* Subject has an hemodynamically significant congenital heart disorder;
* Subject has clinical evidence for infection or active malignancy;
* Subject has known stable chronic kidney dysfunction with serum creatinine \> 2.5 mg/dL at two occasions during the screening period;
* Subject has experienced severe adverse reaction/allergies to contrast agents;
* Subject has atherosclerosis and/or tortuosity of the aorta, iliac or femoral arteries of a degree, that could impede or preclude the safe retrograde passage of the delivery catheter, in the judgment of the investigator;
* Subject is on chronic immunosuppressive transplant therapy;
* Subject had an autologous or allogenic bone marrow or peripheral stem cell transplant or prior solid organ transplantation;
* Subject has a multisystem disease;
* Subject has been tested positive for Human Immunodeficiency Virus (HIV 1 or HIV 2), Hepatitis B Virus (HBV), Hepatitis C (HCV) and/or syphilis;
* Women of child bearing potential;
* Subject has life expectancy \< 1 year from non heart failure related causes;
* Subject suffers from morbid obesity (Body Mass Index (BMI) \> 40);
* Subject has a recent history of alcohol or drug abuse;
* Subject has any other surgical or medical condition that, in the judgment of the investigator might warrant exclusion or be contraindicated for safety reasons;
* Subject is currently participating in another trial.

Answer: B