Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure

Обзор

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.

Вмешательства

• Биопрепарат EHM implantation
  Implantation of EHM on dysfunctional left or right ventricular myocardium in patients with HFrEF (EF \<35%).

Первичные конечные точки

• Adverse events [Срок оценки: 12 months]
• Heart target heart wall thickness [Срок оценки: 12 months]
• LV/RV-ejection fraction [Срок оценки: 12 months]
• Patient reported outcome [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Major adverse cardiac events [Срок оценки: 12 months]
• Arrhythmic events [Срок оценки: 12 months]
• Immune rejection [Срок оценки: 12 months]
• Mechanical perturbation of ventricular function [Срок оценки: 12 months]
• Recurrent hospitalizations for heart failure [Срок оценки: 12 months]
• Mechanical circulatory assist device implantation [Срок оценки: 12 months]
• Heart transplantation [Срок оценки: 12 months]
• Cardiopulmonary stress testing (VO2max) [Срок оценки: 12 months]
• Cardiopulmonary stress testing six-minute walk test (6MWT) [Срок оценки: 12 months]
• Hand-grip strength [Срок оценки: 12 months]
• NYHA classification [Срок оценки: 12 months]
• Quality of life score (EQ-5D-5L) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 3 центра

• University Medical Center Göttingen — Göttingen
• Herz- und Diabeteszentrum Nordrhein-Westfalen — Bad Oeynhausen
• University Medical Center Schleswig-Holstein — Lübeck

Публикации

• 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

Идентификаторы

NCT: NCT04396899 · 02289

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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