Impact of Intracoronary Injection of Autologous BMMC for LV Contractility and Remodeling in Patients With STEMI (RACE-STEMI)

The Impact of Repeated Intracoronary Injection of Autologous Bone-marrow Derived Mononuclear Cells for Left Ventricle Contractility and Remodeling in Patients With STEMI.Prospective Randomized Study.

This is multicentre, randomised open-label, controlled, parallel-group phase III study. Its aim is to demonstrate that a triple intracoronary infusion of autologous bone marrow-derived mononuclear cells in addition to state of the art treatment is safe and reduces all-cause mortality in patients with reduced left ventricular ejection fraction (≤45%) after successful reperfusion for acute myocardial infarction when compared to a control group of patients undergoing best medical care.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Heart Failure
• Intervention / Treatment: Procedure: Intracoronary infusion of BM-MC

Detailed Description

The study is divided into 3 parts:

• Screening phase: Patients will be recruited at the investigational clinical centers. Alternatively, patients who had primary PCI performed at institutions different from the investigational sites can also be enrolled. Interested patients may be referred for screening to any of the participating study sites after acute reperfusion therapy. Informed consent and assessment of eligibility of patients with respect to in- and exclusion criteria will be done at the investigational site. If all other eligibility criteria are met, echocardiography will be performed 3 to 6 days after the acute PCI, and ejection fraction will be quantified by a central Echo Core Lab after web based transmission. CT examination will be performed 1 month after acute PCI in all screened patients with LVEF ≤ 45%. If LVEF will not improve ≥5% in the CT the patient may be qualified into the Study.
• Treatment phase: Bone marrow aspiration will be performed for the patients assigned to the treatment group (II). Bone marrow will be collected from the patient and MNC isolated using point-of-care system (Harvest) at a Site. Intracoronary infusion of BM-MNCs will be performed up to 2 hours after isolation via radial approach. Same procedure will be performed 3 and 6 months after first application.
• Follow-up phase: After hospital discharge, patients will be followed up per telephone 30 days and 3, 6, 9 months after randomisation and with a site visit with CT examination 12 months after randomisation. Afterwards, telephone follow up will be performed every 3 months. Once the required number of clinical events has been observed, all patients will attend a final study visit, but minimum follow up period for each patient is 2 years. Endpoints will be reported as occurring throughout the follow up.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Ustroń, Poland, 43-450
    • Polsko-Amerykanskie Kliniki Serca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Men and women of any ethnic origin aged ≥ 18 years.
2. Patients with acute ST-elevation myocardial infarction as defined by the universal definition of AMI.
3. Successful acute reperfusion therapy (residual stenosis visually <50% and TIMI flow ≥2) within 24 hours of symptom onset or thrombolysis within 12 hours of symptom onset followed by successful percutaneous coronary intervention (PCI) within 24 hours after thrombolysis.
4. Left ventricular ejection fraction ≤ 45% with significant regional wall motion abnormality assessed by quantitative echocardiography (central, independent core lab analysis) 3 to 6 days after reperfusion therapy
5. Open coronary artery suitable for cell infusion supplying the target area of abnormal wall motion
6. LVEF≤45% with significant regional wall motion abnormality assessed by computed tomography (CT) 30 days after reperfusion therapy with no LVEF improvement ≥5%.

Exclusion Criteria:

1. Participation in another clinical trial within 30 days prior to randomisation
2. Previously received stem/progenitor cell therapy
3. Pregnant or nursing women
4. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol
5. Necessity to revascularise additional vessels, outside the target coronary artery at the time of BM-MNC infusion (additional revascularisations after primary PCI and before BM-MNC cell infusion are allowed)
6. Cardiogenic shock requiring mechanical support
7. Platelet count <100,000/μl, or hemoglobin <8.5 g/dl
8. Impaired renal function, i.e. serum creatinine >2.5 mg/dl
9. Persistent fever or diarrhea not responsive to treatment within 4 weeks prior screening
10. Clinically significant bleeding within 3 months prior screening
11. Uncontrolled hypertension (systolic >180 mmHg and diastolic >120 mmHg)
12. Life expectancy of less than 2 years from any non-cardiac cause or neoplastic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care; Optimal standard care after myocardial infarction.
Experimental: Intracoronary infusion of BM-MC; Bone marrow-derived progenitor autologous cells aspiration and intracoronary infusion of the cells.	Procedure: Intracoronary infusion of BM-MC; Bone marrow-derived progenitor cells are obtained from 60ml bone marrow aspirated from the iliac crest. Intracoronary infusion of the autologous cells is performed via conventional percutaneous intracoronary intervention techniques using an over-the-wire balloon technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Left ventricle ejection fraction change evaluated by CT	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in left ventricle End-Systolic Volume (ESV) and End-Diastolic Volume (EDV) evaluated by CT	12 months
Time from randomisation to cardiac death	3 years
Time from randomisation to cardiovascular death or rehospitalisation due to heart failure	3 years
Incidence and severity of adverse events	3 years

Collaborators and Investigators

• Sponsor: American Heart of Poland
• Investigators: Principal Investigator: Pawel E Buszman, MD, PhD, American Heart of Poland

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 18, 2014
• First Submitted That Met QC Criteria: December 18, 2014
• First Posted (Estimate): December 23, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 20, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: cardiovascular disease; stem cells; bone marrow; mortality; Acute myocardial Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: AHP-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No