title: Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.
abstract: OBJECTIVE
  Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy.
  
  
  METHODS
  Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF-related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 10(6) bone marrow-derived and lineage-directed autologous cardiopoietic stem cells administered via a retention-enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months.
  
  
  CONCLUSIONS
  The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF.
  
  
  BACKGROUND
  NCT01768702.
authors.affiliation: Cardiovascular Centre, OLV Hospital, Aalst, Belgium.
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.affiliation: Momentum Research Inc., Durham, NC, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Davison
authors.affiliation: Celyad S.A., Mont Saint Guibert, Belgium.
authors.forename: Warren
authors.initials: W
authors.lastname: Sherman
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Povsic
authors.affiliation: Cedars Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: Mayo Clinic College of Medicine, Division of Cardiovascular Diseases, Department of Medicine, Rochester, MN, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gersh
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Athens University Hospital, Attikon, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Hajjar
authors.affiliation: Mayo Clinic College of Medicine, Division of Cardiovascular Diseases, Department of Medicine, Rochester, MN, USA.
authors.forename: Atta
authors.initials: A
authors.lastname: Behfar
authors.affiliation: Celyad S.A., Mont Saint Guibert, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Homsy
authors.affiliation: Momentum Research Inc., Durham, NC, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Cardiovascular Centre, OLV Hospital, Aalst, Belgium.
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.affiliation: 3rd Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Tendera
authors.affiliation: Mayo Clinic College of Medicine, Division of Cardiovascular Diseases, Department of Medicine, Rochester, MN, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000328:Adult; D002908:Chronic Disease; D015340:Epidemiologic Research Design; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D017202:Myocardial Ischemia / Q000150:complications; D012038:Regeneration; D013234:Stem Cells / Q000502:physiology*
keywords: Cardiopoiesis; Heart failure; Ischaemic cardiomyopathy; Regenerative medicine; Stem cell