Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina
Condition: Refractory Angina
MeSH terms: Angina Pectoris
Intervention: Local sedation; Bone Marrow Aspiration; Minithoracotomy; Autologous bone marrow mononuclear cells infusion
Intervention description: All subjects enrolled in the study underwent local sedation for bone marrow aspiration.; All subjects enrolled in the study underwent bone marrow aspiration after they had been anesthetized from the posterior iliac crest. The sample was aspirated into a series of sterile syringes and brought to the cell processing room/laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines.; The surgical procedure used as cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas.; Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Refractory angina; Cell Therapy; Bone Marrow; Mononuclear Cells

Summary:

      Therapeutic neovascularization is an innovative strategy for cardiac tissue recovery due to
      chronic, intense ischemia. Thus stem cell therapy has become a promising procedure for the
      large number of patients with refractory angina due to coronary disease, despite of the use
      of multiple anti-angina medications, remain severely symptomatic with disabling angina.

      Stem cell therapy using autologous cells from the patient's bone marrow, has been shown to be
      safe and associated with improved myocardial perfusion, reducing the symptoms of advanced
      coronary artery disease and increasing the functional capacity of patients whose therapeutic
      armamentarium available today has been exhausted.

      The study hypothesis was that the infusion of autologous mononuclear cells derived from the
      patient's bone marrow and delivered via intramyocardial injection in patients with refractory
      angina and normal or slightly depressed ventricular function, promote improvement in the
      anginal symptoms and myocardial perfusion by the inducing neoangiogenesis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged above 21 years old;

          -  Documented coronary artery disease by angiography and confirmed ischemia by myocardial
             perfusion scintigraphy with physical or pharmacological stress;

          -  Class IV angina pectoris (CCSAC) that is unresponsive to optimized dose of at least
             two anti-anginal medications including nitrates, beta blocker, calcium channel blocker
             or Ranolazine) as well as aspirin or other anti-platelet agent plus statin therapy;

          -  Considered to not be a candidate for either percutaneous catheter or surgical
             myocardial revascularization due to either anatomical type, extent of coronary disease
             in the target vessel, or caliber of the distal vessels;

          -  Ejection fraction of > 45% by Transthoracic echocardiogram with Doppler by the Simpson
             method;

          -  Myocardial perfusion scintigraphy showing that the areas of myocardial ischemia supply
             viable tissue.

        Exclusion Criteria:

          -  Significant Valvular Heart Disease;

          -  Chronic kidney disease requiring renal replacement therapy;

          -  Severe comorbidities associated with the reduction of life expectancy in less than 5
             years;

          -  Ongoing abusive use of alcohol or illegal drugs (Based on the Diagnostic and
             Statistical Manual (DSM) IV - CAGE questionnaire);

          -  Positive Serologic test for HIV, Human T-cell lymphotrophic virus (HTLV), Hepatitis A,
             B and C;

          -  History of Malignant neoplasia in the last 2 years;

          -  Participation into other studies of cell therapy in the last year;

          -  Pregnancy or Breast-feeding.