Cell Therapy in Myocardial Infarction

Acute Myocardial Infarction Clinical Trial

— EMRTCC  

Official title:

Multicenter Prospective Randomized Double Blind Trial of Bone Marrow Mononuclear Cells Transplantation Through Intracoronary Injection in Patients With Acute Myocardial Infarction.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00350766
• Other study ID #: EMRTCC-IAM
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: July 10, 2006
• Last updated: March 29, 2017
• Start date: July 1, 2006
• Est. completion date: July 14, 2014

Study information

• Verified date: March 2017
• Source: Ministry of Health, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 166
• Est. completion date: July 14, 2014
• Est. primary completion date: January 21, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Procedure:
• Autologous Bone Marrow Mononuclear Cells (ABMMC) Transplantation
Catheter based stem cells delivery of 100 million cells resuspended in a 10 ml solution of saline with autologous serum. About 100 ml of Bone Marrow aspirate were harvested from iliac crest between the fifth and seventh day after myocardial infarction. ABMMC were isolated by density gradient centrifugation on Ficoll-PaqueTM plus (Amersham Biosciences) and manipulated under aseptic conditions for injection, after being filtered through 100 um nylon mesh to remove cell aggregates.

Locations

Country	Name	City	State
Brazil	PROCEP/Hospital Pró-Cardíaco	Rio de Janeiro

Sponsors (30)

Lead Sponsor

Collaborator

Ministry of Health, Brazil

Anis Rassi Hospital, Brazil, Federal University of São Paulo, Federal University of Uberlandia, Hospital Agamenon, Hospital Bandeirantes, Hospital Cardiológico Costantini, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Hospital de Clínicas de Niteroi, Hospital de Clinicas de Porto Alegre, Hospital de Clínicas Mario Lioni, Hospital de Messejana, Hospital do Andaraí, Hospital do Coracao, Hospital Municipal Miguel Couto, Hospital Santa Isabel de Blumenau, Hospital Santa Izabel, Hospital Santa Izabel de Sergipe, Hospital São Marcos, Hospital TotalCor, Hospital Universitário Oswaldo Cruz - UPE, Hospital Universitário Regional do Norte do Paraná - FUEL, InCor Heart Institute, Instituto Dante Pazzanese de Cardiologia, Instituto de Cardiologia do Rio Grande do Sul, Instituto Estadual de Cardiologia Aloysio de Castro, Instituto Nacional de Cardiologia de Laranjeiras, Pro-Cardiaco Hospital, Real Hospital Português de Beneficência, Universidade Federal do Rio de Janeiro

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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, Nóbrega 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Left Ventricular Ejection Fraction change		6 months
Secondary	Death		30 days, 90 days, 6 months and 1 year
Secondary	Acute myocardial infarction, stroke and hospital admission due to cardiovascular cause		30 days, 90 days, 6 months and 1 year
Secondary	Reintervention of the AMI related artery and of the non-related artery		30 days, 90 days, 6 months and 1 year
Secondary	Regional wall motion, wall thickening, and volume of late contrast enhancement		Baseline and 6 months
Secondary	Evolutive alterations of the coronarian anatomy, as well as the patency of the coronary stents		6 months
Secondary	Quality of life assessment using the Short-Form 36, Minnesota Living with Heart Failure Questionnaire and Seattle Angina questionnaire		Baseline, 6 months and 1 year
Secondary	Cost-effectiveness and cost-utility evaluation of autologous bone marrow mononuclear cells implant versus conventional treatment		1 year