ALLOGENEIC INDUCED PLURIPOTENT STEM CELLS-DERIVED CARDIOMYOCYTES AND STROMAL CELLS for Heart failure | Heart failure with reduced ejection fraction (HFrEF)

Inclusion criteria

• {"criterion_text":"- Heart failure with reduced ejection fraction (HFrEF with EF ≤ 35%) as assessed by high-resolution echocardiography and MRI or CT."}
• {"criterion_text":"- At least one hypo- or dyskinetic segment to demark the implant target area."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 18-80 years of age"}
• {"criterion_text":"- Previous implantation of an ICD or CRT-D with event recorder"}
• {"criterion_text":"- New York Heart Association (NYHA) Class III or IV under optimal medical therapy"}
• {"criterion_text":"- Willingness and ability to give written informed consent"}
• {"criterion_text":"- Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety events captured and compared between visit 2 and visit 7 within 28 days; focus on procedure-related adverse events including arrhythmias and disease progression."}
• {"endpoint_text":"- Part B: Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within the whole study duration","definition_or_measurement_approach":"Monitoring and recording of procedure-related adverse events and arrhythmic events over the entire study duration."}
• {"endpoint_text":"- Evidence for structural and functional muscular augmentation of target myocardium determined as enhanced target heart wall thickness (HWT) and thickening fraction (HWTF)","definition_or_measurement_approach":"Structural and functional augmentation assessed by changes in target heart wall thickness (HWT) and heart wall thickening fraction (HWTF) (imaging-based measurements)."}

Secondary endpoints

• {"endpoint_text":"- Frequency of major adverse cardiac events (MACE; non-fatal myocardial infarction, non-fatal stroke and cardiovascular death)","definition_or_measurement_approach":"MACE defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death; incidence/frequency measured during follow-up."}
• {"endpoint_text":"- Frequency and severity of arrhythmic events","definition_or_measurement_approach":"Recording and grading of arrhythmic events (frequency and severity) using monitoring and event recorder data."}
• {"endpoint_text":"- Incidence of immune rejection (allograft DNA, CK/CK-MB, cTnT. DSA)","definition_or_measurement_approach":"Immune rejection assessed by biomarkers including allograft DNA, CK/CK-MB, cTnT, and donor-specific antibodies (DSA)."}
• {"endpoint_text":"- Incidence of mechanical perturbation of ventricular function by EHM graft","definition_or_measurement_approach":"Assessment of ventricular function for mechanical perturbation attributable to EHM graft via imaging and functional tests."}
• {"endpoint_text":"- Recurrent HF hospitalizations","definition_or_measurement_approach":"Tracking of hospital admissions for heart failure during study period."}
• {"endpoint_text":"- Left ventricular ejection fraction (EF)","definition_or_measurement_approach":"Measurement of LVEF by echocardiography/MRI/CT as specified in assessments."}
• {"endpoint_text":"- Change in heart failure medication","definition_or_measurement_approach":"Recording changes in HF medication regimens over time."}
• {"endpoint_text":"- Functional status in patients as determined by cardiopulmonary stress testing (VO2max), six-minute walk test (6MWT), and hand-grip strength measurements","definition_or_measurement_approach":"Functional assessments using VO2max from cardiopulmonary exercise testing, 6MWT distances, and hand-grip strength measures."}
• {"endpoint_text":"- Patient reported outcomes assessed by NYHA classification, quality of life score (KCCQ, EQ-5D, QoL-VAD), and study adherence motivation (PHQ-9, HAF-17, ESSI, LOT-R, ULS-8, medication adherence, Trust/Mistrust in medical staff)","definition_or_measurement_approach":"Patient-reported outcomes via NYHA class, KCCQ, EQ-5D, QoL-VAD and questionnaires including PHQ-9, HAF-17, ESSI, LOT-R, ULS-8 plus adherence and trust measures."}
• {"endpoint_text":"- All-cause and cardiovascular mortality","definition_or_measurement_approach":"Recording of deaths and classification as all-cause or cardiovascular mortality."}

Germany

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

512

Number Of Sites

7

Number Of Participants

53

Primary sponsor

Full Name

Universitaetsmedizin Goettingen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany