Clinical trial NCT00350766: Cell Therapy in Myocardial Infarction
Official title: Multicenter Prospective Randomized Double Blind Trial of Bone Marrow Mononuclear Cells Transplantation Through Intracoronary Injection in Patients With Acute Myocardial Infarction.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Acute Myocardial Infarction
Keywords: Myocardial Infarction
Myocardial Ischemia
Ventricular Remodeling
Bone Marrow Cell Transplantation
Stem cells
Lead sponsor: Ministry of Health, Brazil
Sponsor class: OTHER_GOV
Collaborators: name: Pro-Cardiaco Hospital
name: Hospital do Coracao
name: Instituto Estadual de Cardiologia Aloysio de Castro
name: Hospital Cardiológico Costantini
name: Hospital Universitário Regional do Norte do Paraná - FUEL
name: Hospital Santa Izabel
name: Hospital Santa Izabel de Sergipe
name: Hospital Agamenon
name: Hospital do Andaraí
name: Hospital de Messejana
name: Hospital de Clinicas de Porto Alegre
name: Faculty of Medicine of Ribeirão Preto (FMRP-USP)
name: Instituto Nacional de Cardiologia de Laranjeiras
name: Instituto de Cardiologia do Rio Grande do Sul
name: Hospital São Marcos
name: Hospital Universitário Oswaldo Cruz - UPE
name: Real Hospital Português de Beneficência
name: Hospital Municipal Miguel Couto
name: Anis Rassi Hospital, Brazil
name: Federal University of São Paulo
name: Instituto Dante Pazzanese de Cardiologia
name: Universidade Federal do Rio de Janeiro
name: Hospital Bandeirantes
name: InCor Heart Institute
name: Hospital Santa Isabel de Blumenau
name: Federal University of Uberlandia
name: Hospital TotalCor
name: Hospital de Clínicas Mario Lioni
name: Hospital de Clínicas de Niteroi
First posted: 2006-07-11
Enrollment: 166
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blind Randomized Controlled Trial
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine cell therapy efficacy in patients with ST elevation acute myocardial infarction (STEMI)

Detailed description: This study protocol describes a randomized double blind clinical trial, which main purpose is to evaluate the effect of the autologous bone marrow mononuclear cell (ABMMC) implant in 300 Brazilian patients with ST elevation acute myocardial infarction (STEMI).

Double blind study design was chosen for this trial, based on several phase I and II safety trials of intracoronary autologous bone marrow stem cells transplantation, already published. The study coordinator committee, supported by the Brazilian Health Ministry, therefore has proposed a phase III trial with the purpose of proving the efficacy of this kind of therapy, for a population with a high risk of developing heart failure and of death by cardiovascular cause.

Thus, in this protocol we propose a prospective, double blind, controlled and randomized trial to evaluate the effect of ABMMC transplantation through intracoronary infusion, on systolic left ventricle (LV) function. The main hypothesis of this trial is that patients submitted to autologous bone marrow stem cell implant, after 6 months follow up, will present a 5% relative increase of the ejection fraction (EF) comparing to control group.

Eligibility criteria: Inclusion Criteria:

* Patients will be eligible if presenting all characteristics described below:

  * ST segment elevation myocardial infarction in two or more contiguous leads, and according to the WHO definition, at least one of the following two:

    i) Presence of chest pain. ii) Elevation of the myonecrosis markers.
  * Age between 30 and 80 years old.
  * Ejection fraction ≤50% on Echocardiogram (Simpson) and segmentary dysfunction of the infarction area, measured between the 3rd and 5th day post AMI.

Among patients submitted to thrombolytic therapy, the angioplasty of the related artery should be preferably done up to 24h after thrombolysis, with a maximum deadline of 72h after thrombolysis.

Exclusion Criteria:

* Patients will be ineligible if presenting any of the characteristics described below:

  * AMI related artery presenting TIMI \< 3 at the moment f cell injection.
  * Left Main Coronary Artery Lesion of \>50% or multivessel coronariopathy (\>70% lesion in vessels with \>2,0mm diameter in left anterior descending, circumflex and right coronary territory) indicating the need for CABG or angioplasty with three or more stents implant.
  * Coronary anatomy, after thrombolytic reperfusion, presenting no need for angioplasty with stent implant.
  * Final Diastolic Pression of the LV higher than 30 mmHg during ventriculography for evaluating EF inclusion criteria for the research protocol (item "c" of inclusion criteria).
  * Cardiac arrest or Killip IV AMI at admission with need of ventilatory support.
  * Cardiogenic shock persisting up to the third day after AMI (with need of Intra-aortic balloon pump or vasopressors).
  * AMI mechanical complications (ventricular septal defect, papillary muscle rupture, and left ventricular free wall rupture).
  * Significant valve disease, defined as aortic stenosis (mean systolic pressure gradient across the aortic valve \>50mmHg), mitral stenosis with a valvar area less than 1,5 cm,2 moderate to severe aortic and/or mitral regurgitation.
  * Chronic use of immunosuppressive agents.
  * \> 2,0 mg/dl creatinine or previous dialysis treatment.
  * Presence of fever on the past 48h before injection glaring active systemic infection according to ACCP/SCCM (American College of Chest Physicians/Society of Critical Care Medicine) sepsis definition.
  * Sustained ventricular tachycardia 48h after AMI.
  * Illicit drugs abuse or alcohol abuse (based on DSM IV).
  * Any co morbidity, with survival impact in two years.
  * Myocarditis
  * Active liver disease
  * COPD in continuous steroids use.
  * Hematological disease, neoplasm, bone disease or hemostatic disturbances.
  * Inflammatory disease or chronicle infectious disease.
  * Presence of definitive implantation of a cardiac pace maker or cardiac defibrillator.
  * Impossibility to reach a cells suspension of 100 million mononuclear cells due to cells paucity in the bone marrow aspirate.

Primary outcomes:
measure: Global Left Ventricular Ejection Fraction change
timeFrame: 6 months
Secondary outcomes:
measure: Death
timeFrame: 30 days, 90 days, 6 months and 1 year
measure: Acute myocardial infarction, stroke and hospital admission due to cardiovascular cause
timeFrame: 30 days, 90 days, 6 months and 1 year
measure: Reintervention of the AMI related artery and of the non-related artery
timeFrame: 30 days, 90 days, 6 months and 1 year
measure: Regional wall motion, wall thickening, and volume of late contrast enhancement
timeFrame: Baseline and 6 months
measure: Evolutive alterations of the coronarian anatomy, as well as the patency of the coronary stents
timeFrame: 6 months
measure: Quality of life assessment using the Short-Form 36, Minnesota Living with Heart Failure Questionnaire and Seattle Angina questionnaire
timeFrame: Baseline, 6 months and 1 year
measure: Cost-effectiveness and cost-utility evaluation of autologous bone marrow mononuclear cells implant versus conventional treatment
timeFrame: 1 year
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: PROCEP/Hospital Pró-Cardíaco
Study officials:
affiliation: PROCEP/Pró-Cardíaco Hospital
name: Hans F Dohmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dohmann HF, Silva SA, Sousa AL, Braga AM, Branco RV, Haddad AF, Oliveira MA, Moreira RC, Tuche FA, Peixoto CM, Tura BR, Borojevic R, Ribeiro JP, Nicolau JC, Nobrega AC, Carvalho AC. Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study. Trials. 2008 Jul 3;9:41. doi: 10.1186/1745-6215-9-41.
citation: Tura BR, Martino HF, Gowdak LH, dos Santos RR, Dohmann HF, Krieger JE, Feitosa G, Vilas-Boas F, Oliveira SA, Silva SA, Bozza AZ, Borojevic R, de Carvalho AC. Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study. Trials. 2007 Jan 18;8:2. doi: 10.1186/1745-6215-8-2.