Intramyocardial Transplantation of Bone Marrow Stem Cells in Addition to Coronary Artery Bypass Graft (CABG) Surgery (PERFECT)

July 13, 2020 updated by: Miltenyi Biotec B.V. & Co. KG

Intramyocardial Transplantation of Bone Marrow Stem Cells for Improvement of Post-infarct Myocardial Regeneration in Addition to CABG Surgery: a Controlled, Prospective, Randomized, Double Blinded Multicenter Trial (PERFECT)

In spite of the fact that the post-myocardial infarction survival rate has improved with recent medical advances, reduced heart function attributed to irreversible loss of viable cardiomyocytes is still a major clinical problem.

The aim of the current study is to determine whether intramyocardial injection of autologous CD133+ bone marrow stem cells yields a functional benefit in addition to coronary artery bypass graft (CABG) surgery in patients with chronic ischemic coronary artery disease.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Beginning in 2001, a phase-1 equivalent feasibility and safety evaluation of intramyocardial injection of autologous CD133+ bone marrow cells during elective CABG surgery was conducted at Rostock University. No procedure-related adverse events were observed and there was some improvement of myocardial contractility and perfusion. It was decided to proceed with a controlled efficacy testing, comparing the outcome of standard CABG surgery with that after CABG and CD133+ cell injection. The results of that study indicate that the additional cell injection yields a better left ventricular contractility than CABG alone (LVEF = 47.1±8% vs. 41.3±9% at 6 months). Although this result is encouraging, the trial had several limitations that hamper interpretation of the data. Most notably, no sham-injection of placebo material was performed in the control group, and standard 2D echocardiography served as the only measurement of global LV contractility.

However, there were no procedure-related complications up to 18 months postoperatively, especially no new ventricular arrhythmia or neoplasia.

Therefore, a prospective, double blinded, randomized, and placebo-controlled multi-center trial will be conducted in Germany, employing current state-of-the art measurement of global and regional LV contractility by cardiac MRI. The following hypothesis will be tested: "Patients who undergo CABG & CD133+ cell injection do not have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation". A power analysis based on the previous trial results indicated that 71 patients per group need to be enrolled so as to reject the null-hypothesis with sufficient statistical power. A total of 142 patients will therefore be enrolled in the study. Patients will be randomized in a 1:1 ratio to undergo CABG surgery in conjunction with either intramyocardial injection of autologous CD133-enriched bone marrow cells or placebo. Bone marrow will be harvested one or two days prior to surgery and a CD133-enriched cell product (or placebo) will be prepared at a central cell processing GMP unit. Bypass surgery will be performed and the investigational product will be injected in the border zone of the infarcted myocardium. Random allocation will be performed in the cell production facility, so that neither the patient nor the surgeon nor any of the personnel involved in follow-up examinations will know whether the cell product or placebo was administered. The primary outcome parameter (LVEF at 6 months) will be measured by cardiac MRI, and secondary outcome parameters include physical exercise capacity, cardiac function, safety and Quality of Life (QoL).

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Oeynhausen, Germany, 32545
        • Herz- und Diabeteszentrum Nordrhein Westfalen
      • Berlin, Germany, 13353
        • Deutsches Herzzentrum Berlin
      • Hamburg, Germany, 20246
        • Universitares Herzzentrum Hamburg
      • Hannover, Germany, 30625
        • Medical School Hannover
      • Leipzig, Germany, 04289
        • Herzzentrum Universität Leipzig
      • Rostock, Germany, 18057
        • University of Rostock

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Coronary artery disease after myocardial infarction with indication for CABG surgery
  • Currently reduced global LVEF assessed at site by cardiac MRI at rest (25% ≤ LVEF ≤ 50%)
  • Presence of a localized akinetic/hypokinetic/hypoperfused area of LV myocardium for defining the target area
  • Informed consent of the patient
  • 18 years ≤ Age < 80 years
  • Are not pregnant and do not plan to become pregnant during the study. Females with childbearing potential must provide a negative pregnancy test within 1-7 days before OP and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start).

Exclusion Criteria:

  • Emergency operation
  • Presence of any moderate-severe valvular heart disease requiring concomitant valve replacement or reconstruction
  • Medical History of recent resuscitation in combination with ventricular arrhythmia classified by LOWN ≥ class II
  • Acute myocardial infarction within last 2 weeks
  • Debilitating other disease: Degenerative neurologic disorders, psychiatric disease, terminal renal failure requiring dialysis, previous organ transplantation, active malignant neoplasia, or any other serious medical condition that, in the opinion of the Investigator is likely to alter the patient's course of recovery or the evaluation of the study medication's safety
  • Impaired ability to comprehend the study information
  • Absent informed written consent
  • Treatment with any investigational drug within the previous 30 days
  • Apparent infection (c-reactive protein [CRP] ≥ 20 mg/L, fever ≥ 38.5° C)
  • Contraindication for MRI scan
  • Immune compromise including active infection with Hepatitis B, C, HIV virus or seropositivity for Treponema pallidum
  • Pregnant or breast feeding
  • Childbearing potential with unreliable birth control methods
  • Have previously been enrolled in this study, respectively phase I and phase II
  • Known hypersensitivity or sensitization against murine products and human-anti-mouse-antibody-titer ≥ 1:1000
  • Contraindication to bone marrow aspiration
  • Known hypersensitivity against iron dextran

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Intramyocardial injection of 5 mL of physiological saline + 10% autologous serum intramyocardially during CABG surgery
Active Comparator: CD133+ autologous bone marrow stem cells
Drug: CD133+ autologous bone marrow stem cell
Intramyocardial injection of 5 mL CD133+ cells (0.5-5x10e6 cells) suspended in physiological saline + 10% autologous serum intramyocardially during CABG surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Left ventricular ejection fraction at rest, measured by MRI
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in LVEF as assessed by MRI and echocardiography
Time Frame: early postoperatively and 6 months
early postoperatively and 6 months
Regional contractility in the AOI / Change in LV dimensions (left ventricular end systolic diameter [LVESD], left ventricular end diastolic diameter [LVEDD]) as assessed by echocardiography
Time Frame: early postoperatively (discharge), 6 months
early postoperatively (discharge), 6 months
Physical exercise capacity determined by 6 minute walk test
Time Frame: early postoperatively (discharge), 6 months
early postoperatively (discharge), 6 months
NYHA and CCS class
Time Frame: early postoperatively (discharge), 6 months
early postoperatively (discharge), 6 months
MACE (cardiac death, myocardial infarction, secondary intervention/reoperation, ventricular arrhythmia)
Time Frame: 6 months
6 months
QoL-score: Minnesota Living with Heart Failure Questionnaire, SF36 Questionnaire, EQ-5D Questionnaire
Time Frame: 3 months, 6 months post-OP
3 months, 6 months post-OP

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Miltenyi Biotec B.V. & Co. KG

Collaborators

German Federal Ministry of Education and Research

Investigators

  • Principal Investigator: Gustav Steinhoff, M.D., Universitiy of Rostock

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

July 30, 2009

First Submitted That Met QC Criteria

July 30, 2009

First Posted (Estimate)

July 31, 2009

Study Record Updates

Last Update Posted (Actual)

July 15, 2020

Last Update Submitted That Met QC Criteria

July 13, 2020

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PERFECT 001
  • M-2006-144 (Other Identifier: Sponsor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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