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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.

Phase 1
Conditions
Heart Failure
MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Registration Number
EUCTR2019-000885-39-DE
Lead Sponsor
niversitätsmedizin Göttingen
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
53
Inclusion Criteria

1.Heart failure with reduced ejection fraction (HFrEF with EF = 35%) as assessed by high-resolution echocardiography and MRI or CT.
2.At least one hypo- or dyskinetic segment to demark the implant target area.
3.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, 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).
4.18-80 years of age
5.Previous implantation of an ICD or CRT-D with event recorder
6.New York Heart Association (NYHA) Class III or IV under optimal medical therapy
7.Willingness and ability to give written informed consent
8.Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

1.Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
2.Contraindication to TachoSil® (e.g. hypersenstitivity to human fibrinogen, human thrombin, horse collagen, human albumin, Riboflavin, Natriumchloride, Natriumcitrate, L-Arginin-Hydrochloride)
3.Hypertrophic cardiomyopathy (HCM)
4.Terminal kidney failure (stage 4; GFR <30 ml/min) at the time of enrolment
5.Terminal liver failure (Child-Pugh stage C; score >10) at the time of enrolment
6.Autoimmune disease
7.History of disabling stroke
8.Reduced life expectancy in the short term due to non-cardiac disease
9.Any condition that excludes adherence to study protocol (in particular lack of adherence to prescribed medication)
10.Simultaneous participation in another interventional trial
11.Pregnant or breastfeeding females
12.Known or suspected alcohol and/or drug abuse

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: to assess safety and efficacy of Engineered Human Myocardium (EHM) in patients with terminal heart failure (HFrEF EF <35%) with or without RV dysfunction (TAPSE <16 mm)<br><br><br>;Secondary Objective: to assess effects of EHM-grafts on disease-specific events and symptoms;Primary end point(s): Primary Safety Endpoint<br>•Part A (Dose Escalation steps): Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (based on a comparison of data obtained during visit 2 and visit 7) <br>•Part B: Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within the whole study duration<br><br>Primary efficacy endpoint:<br>•Evidence for structural and functional muscular augmentation of target myocardium determined as enhanced target heart wall thickness (HWT) and thickening fraction (HWTF);Timepoint(s) of evaluation of this end point: 12 months
Secondary Outcome Measures
NameTimeMethod
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