Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: EHM implantation.
- Who it may be relevant to
- Registry conditions: Heart Failure. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Germany
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- Biological EHM implantation
Implantation of EHM on dysfunctional left or right ventricular myocardium in patients with HFrEF (EF \<35%).
Primary outcome measures
- Adverse events [Time frame: 12 months]
- Heart target heart wall thickness [Time frame: 12 months]
- LV/RV-ejection fraction [Time frame: 12 months]
- Patient reported outcome [Time frame: 12 months]
Secondary outcome measures (12)
- Major adverse cardiac events [Time frame: 12 months]
- Arrhythmic events [Time frame: 12 months]
- Immune rejection [Time frame: 12 months]
- Mechanical perturbation of ventricular function [Time frame: 12 months]
- Recurrent hospitalizations for heart failure [Time frame: 12 months]
- Mechanical circulatory assist device implantation [Time frame: 12 months]
- Heart transplantation [Time frame: 12 months]
- Cardiopulmonary stress testing (VO2max) [Time frame: 12 months]
- Cardiopulmonary stress testing six-minute walk test (6MWT) [Time frame: 12 months]
- Hand-grip strength [Time frame: 12 months]
- NYHA classification [Time frame: 12 months]
- Quality of life score (EQ-5D-5L) [Time frame: 12 months]
Eligibility criteria
Inclusion criteria
- 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
- At least one hypo- or dyskinetic segment or dilated heart chamber to demark the implant target area
- (A) Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or (B) open-chest surgery (for RV applications) for a clinically indicated intervention on the LV (e.g., coronary bypass surgery, valve repair, mechanical circulatory support device implantation) with concomitant RV dysfunction, diagnosed using the Tricuspid Annular Plane Systolic Excursion (TAPSE) index <16 mm (Rudski et al. 2010).
- 18-80 years of age
- Willingness and ability to give written informed consent
- Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.
Exclusion criteria
- 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
- Terminal liver failure (Child-Pugh stage C; score >10) at the time of enrolment
- History of disabling stroke
- Reduced life expectancy in the short term due to non-cardiac disease
- Any condition that excludes adherence to study protocol (in particular lack of adherence to prescribed medication)
- Simultaneous participation in another interventional trial
- Pregnant or breastfeeding females
- Known or suspected alcohol and/or drug abuse
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Germany · 3 centers
- University Medical Center Göttingen — Göttingen
- Herz- und Diabeteszentrum Nordrhein-Westfalen — Bad Oeynhausen
- University Medical Center Schleswig-Holstein — Lübeck
Publications
- Zimmermann WH, Ensminger S, Kutschka I, Paitazoglou C, Seidler T, Brandenburg S, Anker SD, Bader N, Bergau L, Bremmer F, Diogo PG, Eitel I, Fujita B, Gerecke B, Hasenfuss G, Hellenkamp K, Hermann-Lingen C, Jebran AF, Jurczyk D, Knaus R, Legler T, Lotz J, Placzek M, Puhler T, Riggert J, Sadlonova M, Saraei R, Strobel P, Tiburcy M, Ullrich C, Voigt JU, Walker F, Wollnik B, Yigit G, Friede T; BioVAT- PMID 42202318
- Montague EC, Ozcan B, Sefton E, Wulkan F, Alibhai FJ, Laflamme MA. Human pluripotent stem cell-based cardiac repair: Lessons learned and challenges ahead. Adv Drug Deliv Rev. 2025 Jul;222:115594. doi: 10.1016/j.addr.2025.115594. Epub 2025 May 5. PMID 40334814
Identifiers
NCT: NCT04396899 · 02289