Cell Therapy in Myocardial Infarction (EMRTCC)

• ClinicalTrials.gov Identifier: NCT00350766
• Recruitment Status: Terminated
• First Posted: July 11, 2006
• Last Update Posted: March 30, 2017
• Sponsor: Ministry of Health, Brazil
• Collaborators: Pro-Cardiaco Hospital; Hospital do Coracao; Instituto Estadual de Cardiologia Aloysio de Castro; Hospital Cardiológico Costantini; Hospital Universitário Regional do Norte do Paraná - FUEL; Hospital Santa Izabel; Hospital Santa Izabel de Sergipe; Hospital Agamenon; Hospital do Andaraí; Hospital de Messejana; Hospital de Clinicas de Porto Alegre; Faculty of Medicine of Ribeirão Preto (FMRP-USP); Instituto Nacional de Cardiologia de Laranjeiras; Instituto de Cardiologia do Rio Grande do Sul; Hospital São Marcos; Hospital Universitário Oswaldo Cruz - UPE; Real Hospital Português de Beneficência; Hospital Municipal Miguel Couto; Anis Rassi Hospital, Brazil; Federal University of São Paulo; Instituto Dante Pazzanese de Cardiologia; Universidade Federal do Rio de Janeiro; Hospital Bandeirantes; InCor Heart Institute; Hospital Santa Isabel de Blumenau; Federal University of Uberlandia; Hospital TotalCor; Hospital de Clínicas Mario Lioni; Hospital de Clínicas de Niteroi
• Information provided by (Responsible Party): Hans Fernando Rocha Dohmann, Pro-Cardiaco Hospital

Tracking Information

• First Submitted Date: July 10, 2006
• First Posted Date: July 11, 2006
• Last Update Posted Date: March 30, 2017
• Actual Study Start Date: July 1, 2006
• Actual Primary Completion Date: January 21, 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 19, 2007): Global Left Ventricular Ejection Fraction change [ Time Frame: 6 months ]
• Original Primary Outcome Measures (submitted: July 10, 2006): Primary outcome is the difference of the ejection fraction evaluation between groups comparing in hospital phase and 6 months follow up.

Current Secondary Outcome Measures (submitted: March 29, 2017)

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

Original Secondary Outcome Measures (submitted: July 10, 2006)

• Compare the following variables in the treatment and control groups:
• Death for any reason,
• Death for cardiovascular reason,
• Hospital admission due to angina,
• Acute myocardial infarction related to cells implant, defined as CPK elevation three times over the normal value, comparing to normal value (TIMI 18 criteria,
• Hospital admission for heart failure,
• Reintervention of the target lesion,
• Reintervention of the AMI related artery,
• Reintervention of the non related artery,
• Acute myocardial infarction,
• Stroke,
• Main cardiac adverse events (MACE): Death for cardiovascular reason; hospital admission due to angina, AMI or heart failure; Reintervention of the AMI related artery; Reintervention of the target lesion,
• Percentage of patients with 5% absolute improvement of the EF%, evaluated by MRI,
• Segmentary contractility of the LV, evaluated by echocardiogram,
• Systolic and diastolic final volumes by the echocardiogram,
• LV systolic and diastolic final volumes evaluated by cardiac MRI,
• LV diastolic function by the echocardiogram,
• Infarct size and left ventricular wall transmurality studied by performing gadolinium.cardiac magnetic resonance imaging, first-pass perfusion, and delayed enhancement imaging,
• Evolutive alterations of the coronarian anatomy, as well as the patency of the coronary stents, by the coronary angiography and USIC (coronary ultrasound),
• Heart failure and angina symptoms according to NYHA and CCSC class, respectively,
• Quality of life assessment using the Short-Form 36, Minnesota Living with Heart Failure Questionnaire and Seattle Angina questionnaire,
• LV systolic function of the following subgroups: primary angioplasty or fibrinolytics; male or female; elderly (>65 years old) or not; diabetic or not diabetic; hyperglycemia (>125 mg/dl) or not; hypercholesterolemia ( LDL 100-130 mg/dl; LDL 130-160 m
• - Cost effectiveness evaluation of autologous bone marrow mononuclear cells implant versus conventional treatment in patients with AMI, during the period of 1 year

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double Blind Randomized Controlled Trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Control group received injection of saline with 5% autologous serum without the suspension of mononuclear cells.

Primary Purpose: Treatment

• Condition: Acute 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.

Other Name: Catheter based stem cell delivery

Study Arms

• Experimental: Treated Group
  Intracoronary injection in the infarcted-related artery of 100 million bone marrow mononuclear cells resuspended in a 10 ml solution of saline with autologous serum.
  Intervention: Procedure: Autologous Bone Marrow Mononuclear Cells (ABMMC) Transplantation
• Placebo Comparator: Control Group
  Intracoronary injection in the infarcted-related artery of placebo solution consisting of a saline containing autologous blood serum.
  Intervention: Procedure: Autologous Bone Marrow Mononuclear Cells (ABMMC) Transplantation

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 29, 2017): 166
• Original Enrollment (submitted: July 10, 2006): 300
• Actual Study Completion Date: July 14, 2014
• Actual Primary Completion Date: January 21, 2014 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT00350766
• Other Study ID Numbers: EMRTCC-IAM
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Hans Fernando Rocha Dohmann, Pro-Cardiaco Hospital
• Original Responsible Party: Not Provided
• Current Study Sponsor: Ministry of Health, Brazil
• Original Study Sponsor: Same as current

Collaborators

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

Investigators

• Principal Investigator: Hans F Dohmann, MD; PROCEP/Pró-Cardíaco Hospital

• PRS Account: Ministry of Health, Brazil
• Verification Date: March 2017