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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Miltenyi Biotec GmbH
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Miltenyi Biotec GmbH
ClinicalTrials.gov Identifier:
NCT00950274
First received: July 30, 2009
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Myocardial Ischemia
Coronary Artery Disease
Drug: CD133+ autologous bone marrow stem cell
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Miltenyi Biotec GmbH:

Primary Outcome Measures:
  • Left ventricular ejection fraction at rest, measured by MRI [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in LVEF as assessed by MRI and echocardiography [ Time Frame: early postoperatively and 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Physical exercise capacity determined by 6 minute walk test [ Time Frame: early postoperatively (discharge), 6 months ] [ Designated as safety issue: No ]
  • NYHA and CCS class [ Time Frame: early postoperatively (discharge), 6 months ] [ Designated as safety issue: No ]
  • MACE (cardiac death, myocardial infarction, secondary intervention/reoperation, ventricular arrhythmia) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • QoL-score: Minnesota Living with Heart Failure Questionnaire, SF36 Questionnaire, EQ-5D Questionnaire [ Time Frame: 3 months, 6 months post-OP ] [ Designated as safety issue: No ]

Estimated Enrollment: 142
Study Start Date: July 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Drug: Placebo
Intramyocardial injection of 5 mL of physiological saline + 10% autologous serum intramyocardially during CABG surgery

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).

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950274

Contacts
Contact: Gustav Steinhoff, M.D. +49 381 494 6100 gustav.steinhoff@med.uni-rostock.de

Locations
Germany
Herz- und Diabeteszentrum Nordrhein Westfalen Recruiting
Bad Oeynhausen, Germany, 32545
Contact: Jochen Börgermann, MD    +49 5731 97 ext 32 47    jboergermann@hdz-nrw.de   
Principal Investigator: Jochen Börgermann, MD         
Deutsches Herzzentrum Berlin Recruiting
Berlin, Germany, 13353
Contact: Roland Hetzer, MD         
Principal Investigator: Roland Hetzer, MD         
Universitäres Herzzentrum Hamburg Recruiting
Hamburg, Germany, 20246
Contact: Florian M. Wagner, MD         
Principal Investigator: Florian M. Wagner, MD         
Medical School Hannover Recruiting
Hannover, Germany, 30625
Contact: Ingo Kutschka, M.D.       Kutschka.Ingo@MH-Hannover.DE   
Principal Investigator: Axel Haverich, MD         
Herzzentrum Universität Leipzig Recruiting
Leipzig, Germany, 04289
Contact: Jens Garbade, MD    +49 3418651 ext 570    jens.garbade@herzzentrum-leipzig.de   
Principal Investigator: Friedrich-Wilhelm Mohr, MD         
University of Rostock Recruiting
Rostock, Germany, 18057
Contact: Gustav Steinhoff, M.D.    +49 381 494-6100    gustav.steinhoff@med.uni-rostock.de   
Principal Investigator: Gustav Steinhoff, MD         
Sponsors and Collaborators
Miltenyi Biotec GmbH
German Federal Ministry of Education and Research
Investigators
Principal Investigator: Gustav Steinhoff, M.D. Universitiy of Rostock
  More Information

No publications provided by Miltenyi Biotec GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Miltenyi Biotec GmbH
ClinicalTrials.gov Identifier: NCT00950274     History of Changes
Other Study ID Numbers: PERFECT 001, M-2006-144
Study First Received: July 30, 2009
Last Updated: December 9, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Miltenyi Biotec GmbH:
Cell therapy
Bone marrow
CD133
Bypass surgery
Stem cells
Myocardial infarction
Myocardial ischemia

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Ischemia
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014