Clinical trial NCT04396899: Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
Official title: Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: University Medical Center Freiburg
name: Repairon GmbH
First posted: 2020-05-21
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Target heart wall thickness
timeFrame: 12 months
measure: Heart wall thickening fraction
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
state: Lower Saxony
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen
state: North Rhine-Westphalia
city: Lübeck
country: Germany
facility: University Medical Center Schleswig-Holstein
state: Schleswig-Holstein
Study officials:
affiliation: University Medical Center Goettingen
name: Tim Seidler, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Goettingen
name: Wolfram-Hubertus Zimmermann, Prof.
role: STUDY_DIRECTOR
References: