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

NCT00950274 | Terminated Phase 3 DMC

• 2 other identifiers: PERFECT 001M-2006-144
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Myocardial Ischemia; Coronary Artery Disease

Keywords

Cell therapy; Bone marrow; CD133; Bypass surgery; Stem cells; Myocardial infarction; Myocardial ischemia

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction at rest, measured by MRI

  6 months

Secondary Outcomes (6)

• Change in LVEF as assessed by MRI and echocardiography

  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

  early postoperatively (discharge), 6 months

• Physical exercise capacity determined by 6 minute walk test

  early postoperatively (discharge), 6 months

• NYHA and CCS class

  early postoperatively (discharge), 6 months

• MACE (cardiac death, myocardial infarction, secondary intervention/reoperation, ventricular arrhythmia)

  6 months

Study Arms (2)

CD133+ autologous bone marrow stem cells

ACTIVE COMPARATOR

Drug: CD133+ autologous bone marrow stem cell

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CD133+ autologous bone marrow stem cell DRUG

Intramyocardial injection of 5 mL CD133+ cells (0.5-5x10e6 cells) suspended in physiological saline + 10% autologous serum intramyocardially during CABG surgery

CD133+ autologous bone marrow stem cells

Placebo DRUG

Intramyocardial injection of 5 mL of physiological saline + 10% autologous serum intramyocardially during CABG surgery

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Miltenyi Biotec B.V. & Co. KG: lead
• German Federal Ministry of Education and Research: collaborator

Study Sites (6)

Herz- und Diabeteszentrum Nordrhein Westfalen

Bad Oeynhausen, 32545, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, 13353, Germany

Location

Universitäres Herzzentrum Hamburg

Hamburg, 20246, Germany

Location

Medical School Hannover

Hanover, 30625, Germany

Location

Herzzentrum Universität Leipzig

Leipzig, 04289, Germany

Location

University of Rostock

Rostock, 18057, Germany

Location

Related Publications (3)

• Wolfien M, Klatt D, Salybekov AA, Ii M, Komatsu-Horii M, Gaebel R, Philippou-Massier J, Schrinner E, Akimaru H, Akimaru E, David R, Garbade J, Gummert J, Haverich A, Hennig H, Iwasaki H, Kaminski A, Kawamoto A, Klopsch C, Kowallick JT, Krebs S, Nesteruk J, Reichenspurner H, Ritter C, Stamm C, Tani-Yokoyama A, Blum H, Wolkenhauer O, Schambach A, Asahara T, Steinhoff G. Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3. EBioMedicine. 2020 Jul;57:102862. doi: 10.1016/j.ebiom.2020.102862. Epub 2020 Jul 4.

  PMID: 32629392 DERIVED

• Steinhoff G, Nesteruk J, Wolfien M, Kundt G; PERFECT Trial Investigators Group; Borgermann J, David R, Garbade J, Grosse J, Haverich A, Hennig H, Kaminski A, Lotz J, Mohr FW, Muller P, Oostendorp R, Ruch U, Sarikouch S, Skorska A, Stamm C, Tiedemann G, Wagner FM, Wolkenhauer O. Cardiac Function Improvement and Bone Marrow Response -: Outcome Analysis of the Randomized PERFECT Phase III Clinical Trial of Intramyocardial CD133+ Application After Myocardial Infarction. EBioMedicine. 2017 Aug;22:208-224. doi: 10.1016/j.ebiom.2017.07.022. Epub 2017 Jul 29.

  PMID: 28781130 DERIVED

• Donndorf P, Kaminski A, Tiedemann G, Kundt G, Steinhoff G. Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial. Trials. 2012 Jul 2;13:99. doi: 10.1186/1745-6215-13-99.

  PMID: 22747980 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia; Coronary Artery Disease; Myocardial Infarction

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Gustav Steinhoff, M.D.

  Universitiy of Rostock

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: July 1, 2009
• Primary Completion: March 1, 2016
• Study Completion: September 1, 2017
• Last Updated: July 15, 2020

Record last verified: 2018-08

Locations

DE (6)