Clinical trial NCT00362388: Cell Therapy in Chronic Ischemic Heart Disease
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Intramyocardial Injection of Autologous Bone-Marrow Cells in Patients With Severe, Chronic Ischemic Heart Disease Undergoing Coronary Bypass Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ischemic Heart Disease
Coronary Artery Disease
Keywords: Coronary artery disease
Ischemic heart disease
Angiogenesis
Cells
Cardiac surgery
Lead sponsor: Ministry of Health, Brazil
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Science and Technology
First posted: 2006-08-10
Enrollment: 300
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to test the hypothesis that direct injection of bone-marrow cells in the heart may increase the number of blood vessels, ameliorating the heart's performance, and relieving patients from symptoms like angina and/or shortness of breath.

Detailed description: Severe ischemic heart disease (IHD) remains a clinical challenge; many patients with IHD have undergone myocardial revascularization procedures (either percutaneous or surgical) but still remain symptomatic despite maximally tolerated medical therapy. Others are considered non-optimal candidates for a complete myocardial revascularization procedure due to the extension and diffuseness of the disease.

Cell therapy with autologous bone marrow-derived cells (BMC) is a novel therapeutic strategy being tested for many cardiovascular diseases, including heart failure, acute myocardial infarction, chronic ischemic heart disease.

The primary objective of this study is to assess the efficacy of intramyocardial injection of autologous BMC on the myocardial perfusion and left ventricular function as an adjunctive therapy (compared to placebo) in patients undergoing coronary artery bypass surgery (CABG).

The secondary objective of this study is to assess the effect of intramyocardial injection of autologous BMC on functional class (angina/heart failure), functional capacity, global and cardiovascular mortality, and quality of life in patients undergoing coronary artery bypass surgery (CABG).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of chronic, severe, diffuse, multivessel atherosclerotic coronary artery disease (CAD) referred for CABG.
* Echocardiogram-assessed LVEF between 25 and 55% (Simpson's rule).
* Angina (or equivalent) functional class II to IV (Canadian Cardiovascular Society) despite maximally tolerated medical therapy.
* Abnormal myocardial perfusion tests:

  i. Cardiac scintigraphy ii. Magnetic resonance imaging iii. Dobutamine-atropine stress-echocardiogram
* Non-candidates for a percutaneous coronary intervention (PCI) due to ANY of the following:

  i. High risk lesion ii. Extensive lesion iii. Diffuse, small vessel disease
* Non-candidates for a complete CABG, or candidates for a complete CABG in whom, according to an expert panel, there is a high probability of failure of the grafts due to the extension and severity of the disease, with diffuse, small vessel involvement.
* To provide a signed, written informed consent, according to the National Guidelines for Clinical Trials.

Exclusion Criteria:

* Severe valve heart disease requiring surgical repair.
* Serologic diagnostic of Chagas' disease.
* Symptoms of heart failure, even from an ischemic etiology, in the absence of objectively documented myocardial ischemia.
* Malignant ventricular arrhythmias (like VT), unless an ICD have been placed.
* Any acute coronary syndrome in the past 3 months.
* End-stage renal disease requiring maintenance dialysis.
* History of neoplasia.
* Drug or alcohol abuse.
* Life expectancy below 2 years.
* Enrollment in any cell therapy trial in the past 2 years.

Primary outcomes:
measure: Reduction in the ischemic score (global/regional) at 12 months; increase in left ventricle ejection fraction (LVEF) at 12 months.
Secondary outcomes:
measure: All-cause and cardiovascular mortality during the first year; increase in VO2max, increase in quality of life, reduction in angina/heart failure functional class at 12 months; percentage of patients with a 5% increase in LVEF at 6 and 12 months.
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Instituto do Coração de Pernambuco do Real Hospital Português de Beneficência
state: PE
city: Curitiba
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia
state: PR
city: Curitiba
country: Brazil
facility: Clínica Cardiologyca C. Constantini
state: PR
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cardiologia Laranjeiras (INCL)
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Hospital Pró-Cardíaco
state: RJ
city: São Paulo
country: Brazil
facility: Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School
state: SP
Study officials:
affiliation: Heart Institute (InCor), Hospital das Clinicas, University of São Paulo Medical School
name: Sergio A. de Oliveira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Institute (InCor), Hospital das Clinicas, University of São Paulo Medical School
name: Jose Eduardo Krieger, MD, PhD
role: STUDY_DIRECTOR
References: