Cell Therapy in Severe Chronic Ischemic Heart Disease (MiHeart)

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

Patients with advanced coronary artery disease usually undergo incomplete myocardial revascularization due to the extension and diffuseness of the disease, with very poor distal arterial beds unsuitable for direct revascularization.

This study was designed to test the hypothesis that direct, intramyocardial injection of autologous bone marrow cells may further improve myocardial perfusion in patients undergoing incomplete bypass surgery.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Angina Pectoris; Chronic Ischemic Heart Disease
• Intervention / Treatment: Procedure: Cell Therapy

Detailed Description

All eligible patients will undergo coronary artery bypass grafting (CABG) and, in previously identified areas of viable, ischemic myocardium unsuitable for direct revascularization, be randomized to either placebo (saline) or intramyocardial injection of bone marrow-derived cells (BMC) during surgery.

During follow-up, myocardial perfusion assessment will be performed to determine the improvement in treated areas compared to non-treated segments.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• symptoms of angina or angina equivalent
• documented coronary artery disease (invasive angiography)
• documented myocardial ischemia (stress echo, cardiac scintigraphy, or MRI)
• unsuitable for complete myocardial revascularization (PCI or CABG) OR even if a complete procedure in feasible, it is anticipated that myocardial perfusion may not be restored due to poor distal beds

Exclusion Criteria:

• severe LV dysfunction (EF < 25% on echo)
• short life expectacy (below < 1 year)
• diagnosis of cancer in the past 5 years
• diagnosis of hematological diseases
• diagnosis of severe heart disease of other etiologies including valvular heart disease, Chagas' disease, etc)
• diagnosis of acute coronary syndrome in the past 3 months
• diagnosis of chronic kidney disease stage V requiring chronic dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cell Therapy; Intramyocardial injection of autologous bone marrow-derived cells	Procedure: Cell Therapy; Intramyocardial injection of autologous bone marrow-derived cells
No Intervention: Placebo; Saline injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in myocardial perfusion	Patients will undergo myocardial perfusion assessment by MRI during pharmacological stress with adenosine or dipyridamole. Alternatively, cardiac scintigraphy can be used in patients with contra-indications to MRI.	1, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in LV function	LV function (global and regional) will be assessed by MRI.	1, 6 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in angina functional class	Angina functional class will be determined using the Canadian Cardiovascular Society classification.	1, 6 and 12 months

Collaborators and Investigators

• Sponsor: Ministry of Health, Brazil
• Investigators: Study Director: Jose Eduardo Krieger, MD, PhD, Heart Institute; Study Chair: Carlos Eduardo Rochitte, MD, PhD, Heart Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: November 12, 2012
• First Submitted That Met QC Criteria: November 12, 2012
• First Posted (Estimate): November 15, 2012

Study Record Updates

• Last Update Posted (Actual): August 30, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Coronary artery disease; Cardiac surgery; Angina pectoris; Myocardial ischemia; Chronic ischemic heart disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Chest Pain; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia; Angina Pectoris
• Other Study ID Numbers: EMRTCC-ISQ2