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

Phase 2RecruitingNCT04396899

University Medical Center Goettingen53 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heart Failure

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Symptomatic heart failure (NYHA II-IV) with reduced ejection fraction (HFrEF with LVEF ≤35%) as assessed by echocardiography. 2. Patients on guideline-directed medical therapy 3. NT-proBNP \>300 pg/mL for patients in sinus rhythm or \>900 pg/mL if in atrial fibrillation 4. History of previous heart failure hospitalization in the past 12 months 5. At least one hypo- or dyskinetic segment or dilated heart chamber to demark the implant target area 6. (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). 7. 18-80 years of age 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. Contraindication to TachoSil® (e.g. hypersensitivity 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. History of disabling stroke 7. Reduced life expectancy in the short term due to non-cardiac disease 8. Any condition that excludes adherence to study protocol (in particular lack of adherence to prescribed medication) 9. Simultaneous participation in another interventional trial 10. Pregnant or breastfeeding females 11. Known or suspected alcohol and/or drug abuse

Locations (3)

University Medical Center Göttingen

Göttingen, Lower Saxony, Germany

RECRUITING

Herz- und Diabeteszentrum Nordrhein-Westfalen

Bad Oeynhausen, North Rhine-Westphalia, Germany

NOT_YET_RECRUITING

University Medical Center Schleswig-Holstein

Lübeck, Schleswig-Holstein, Germany

RECRUITING

Outcomes

Primary Outcomes

Adverse events

Number of Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (Part A) and the whole study duration (Part B)

Time frame: 12 months

Heart target heart wall thickness

Change of target heart wall thickness (TWTh in mm) Echo or cCT or cMRI

Time frame: 12 months

LV/RV-ejection fraction

Change of LV/RV-ejection fraction (LV/RV-EF in %) Echo or cCT or cMRI

Time frame: 12 months

Patient reported outcome

Patient reported outcome Change of KCCQ-23 OSS (Overall Summary Score)

Time frame: 12 months

Secondary Outcomes

Major adverse cardiac events

Frequency of major adverse cardiac events (MACE; non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death)

Time frame: 12 months

Arrhythmic events

Frequency and severity of arrhythmic events

Time frame: 12 months

Immune rejection

Incidence of immune rejection (DSA, CK/CK-MB, hs-cTnT, circulating cell-free allograft DNA)

Time frame: 12 months

Mechanical perturbation of ventricular function

Incidence of mechanical perturbation of ventricular function by EHM graft

Time frame: 12 months

Recurrent hospitalizations for heart failure

Frequency of recurrent hospitalizations for heart failure

Time frame: 12 months

Mechanical circulatory assist device implantation

Time to mechanical circulatory assist device implantation

Time frame: 12 months

Heart transplantation

Time to heart transplantation.

Time frame: 12 months

Cardiopulmonary stress testing (VO2max)

Functional status in patients as determined by cardiopulmonary stress testing (VO2max)

Time frame: 12 months

Cardiopulmonary stress testing six-minute walk test (6MWT)

Functional status in patients as determined by cardiopulmonary stress testing six-minute walk test (6MWT) - distance (in m)

Time frame: 12 months

Hand-grip strength

Functional status in patients as determined by and hand-grip strength measurements

Time frame: 12 months

NYHA classification

Patient reported outcomes assessed by NYHA classification

Time frame: 12 months

Quality of life score (EQ-5D-5L)

Patient reported outcomes assessed by quality of life score (EQ-5D-5L)

Time frame: 12 months

Hospital Anxiety and Depression Scale (HADS)

Patient reported outcomes assessed by study adherence motivation according to following questionnaire: HADS

Time frame: 12 months

Mortality

All-cause and cardiovascular mortality

Time frame: 12 months

Montreal Cognitive Assessment (MoCA)

Patient reported outcomes assessed by study adherence motivation according to following questionnaire: MoCA

Time frame: 12 months

Medication adherence

Patient reported outcomes assessed by study adherence motivation according to medication adherence questionnaire.

Time frame: 12 months

Brief Illness Perception Questionnaire (B-IPQ)

Patient reported outcomes assessed by study adherence motivation according to following questionnaire: B-IPQ

Time frame: 12 months

Treatment Expectation Questionnaire (TEX-Q)

Patient reported outcomes assessed by study adherence motivation according to following questionnaire: TEX-Q

Time frame: 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts