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

Phase 1

Recruiting

• Conditions: Heart Failure
• Interventions: Biological: EHM implantation

• Registration Number: NCT04396899
• Lead Sponsor: University Medical Center Goettingen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-02-03
• Study First Submitted: 2020-05-11
• Study First Submitted QC: 2020-05-15
• Study First Posted: 2020-05-21
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

1. HFrEF (EF ≤ 35%) as assessed by high-resolution echocardiography or MRI
2. No realistic chance or not eligible for heart transplantation
3. At least one hypo- or dyskinetic segment to demark the implant target area
4. Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or open-chest surgery (for RV applications) for a clinically indicated intervention on the LV (e.g., coronary bypass surgery, valve repair) with concomitant RV dysfunction, diagnosed using the Tricuspid Annular Plane Systolic Excursion (TAPSE) index <16 mm (Rudski et al. 2010).
5. 18-80 years of age
6. Previous implantation of an ICD or CRT-D with event recorder
7. New York Heart Association (NYHA) Class III or IV under optimal medical therapy
8. Willingness and ability to give written informed consent
9. Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.

Exclusion Criteria

1. Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
2. Alloimmunisation against EHM implant cells
3. Hypertrophic cardiomyopathy (HCM)
4. Terminal kidney failure (stage 4; GFR <30 ml/min)
5. Terminal liver failure
6. Autoimmune disease
7. History of stroke
8. Reduced life expectancy in the short term due to non-cardiac disease
9. Simultaneous participation in another interventional trial
10. Pregnant or breastfeeding females
11. Known or suspected alcohol and/or drug abuse

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EHM Implantation	EHM implantation	All patients will receive EHM implant

Primary Outcome Measures

Name	Time	Method
Target heart wall thickness	12 months	Target heart wall thickness (HWT) as determined by high resolution echocardiography and/or CINE-mode MRI (17-segment model). Primary efficacy analyses are based on the changes in HWT between baseline and 2 weeks, 1 month, 3 months, 6 months and 12 months after implantation. To test for a time effect a one-way Repeated Measures ANOVA will be performed for the primary endpoint. In case of detecting a time effect this is followed by Dunnett-type pairwise comparisons to baseline using paired t-Tests. Due to the explorative character of the efficacy analysis testing will be performed at a 10% two-sided significance level. Mean differences will be reported along with 90% confidence intervals.
Heart wall thickening fraction	12 months	Heart wall thickening fraction (HWTF) as determined by high resolution echocardiography and/or CINE-mode MRI (17-segment model). Primary efficacy analyses are based on the changes in HWTF between baseline and 2 weeks, 1 month, 3 months, 6 months and 12 months after implantation. To test for a time effect a one-way Repeated Measures ANOVA will be performed for the primary endpoint. In case of detecting a time effect this is followed by Dunnett-type pairwise comparisons to baseline using paired t-Tests. Due to the explorative character of the efficacy analysis testing will be performed at a 10% two-sided significance level. Mean differences will be reported along with 90% confidence intervals.

Trial Locations

Locations (3)

University Medical Center Göttingen; 🇩🇪 Göttingen, Lower Saxony, Germany

Herz- und Diabeteszentrum Nordrhein-Westfalen; 🇩🇪 Bad Oeynhausen, North Rhine-Westphalia, Germany

University Medical Center Schleswig-Holstein; 🇩🇪 Lübeck, Schleswig-Holstein, Germany