The BioVAT-HF trial will test the hypothesis that cardiomyocyte implantation via engineered heart muscle (EHM), the proposed investigational medicinal product (IMP; designated "Biological Ventricular Assist Tissue" or BioVAT), results in sustainable remuscularization and biological enhancement of myocardial performance in the failing heart. EHM are constructed from defined mixtures of induced pluripotent stem cell (iPSC)-derived cardiomyocytes and stromal cells in a bovine collagen type I hydrogel. Comprehensive preclinical testing confirmed the rationale for the clinical translation of the myocardial remuscularization strategy by EHM implantation. The patient target population for EHM therapy is patients suffering from advanced heart failure with reduced ejection fraction (HFrEF; EF: ≤35%) and no realistic option for heart transplantation.
Symptomatic heart failure (NYHA II-IV) with reduced ejection fraction (HFrEF with LVEF ≤35%) as assessed by echocardiography.
Patients on guideline-directed medical therapy
NT-proBNP >300 pg/mL for patients in sinus rhythm or >900 pg/mL if in atrial fibrillation
History of previous heart failure hospitalization in the past 12 months
Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
Contraindication to TachoSil® (e.g. hypersensitivity to human fibrinogen, human thrombin, horse collagen, human albumin, Riboflavin, Natriumchloride, Natriumcitrate, L-Arginin-Hydrochloride)
Hypertrophic cardiomyopathy (HCM)
Terminal kidney failure (stage 4; GFR <30 ml/min) at the time of enrolment
Single group
EHM implantation
Biological/VaccineImplantation of EHM on dysfunctional left or right ventricular myocardium in patients with HFrEF (EF \<35%).
Adverse events
Number of Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (Part A) and the whole study duration (Part B)
Heart target heart wall thickness
Change of target heart wall thickness (TWTh in mm) Echo or cCT or cMRI
LV/RV-ejection fraction
Change of LV/RV-ejection fraction (LV/RV-EF in %) Echo or cCT or cMRI
Patient reported outcome
Patient reported outcome Change of KCCQ-23 OSS (Overall Summary Score)
Major adverse cardiac events
Frequency of major adverse cardiac events (MACE; non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death)
Arrhythmic events
Frequency and severity of arrhythmic events
Immune rejection
Incidence of immune rejection (DSA, CK/CK-MB, hs-cTnT, circulating cell-free allograft DNA)
Mechanical perturbation of ventricular function
Incidence of mechanical perturbation of ventricular function by EHM graft
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University Medical Center Goettingen
Lead sponsor
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Collaborator
University Medical Center Freiburg
Collaborator
Repairon GmbH
Collaborator
