Clinical trial NCT05809856: Feasibility Study to Evaluate the Safety of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve
Official title: A First-in-Human Feasibility Study to Evaluate the Safety (and Short Term Effectiveness) of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve [GECT]
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pulmonary Valve Insufficiency
Keywords: Heart Valve Replacement
Pulmonary Valve
Congenital Heart Diseases
Transcatheter Valve
Medical Need
Durable
One-time-solution
Autologous Living Tissue
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 7
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
Intervention model description: Non-inferiority analysis with standard of current medical care
Primary purpose: TREATMENT

Brief summary: Aim of this study is to investigate the clinical safety of a novel pediatric heart valve.

Detailed description: Defective or diseased pulmonary heart valves do not recover. If left untreated, pediatric and adult patients alike, face serious risks of progressive heart failure and death. Due to the insufficient care of children with heart valve defects, the valve replacement with regenerative, remodeling, and growth potential remains an unmet medical need. Therefore, the first pediatric heart valve (GrOwnValve) was developed to overcome the current limitations, which should offer regenerative potential that adapts to the somatic growth of the child. The study aims to investigate the safety and provide the first initial efficacy estimates of the transcatheter implantable GrOwnValve. This first prospective, non-randomized, single center trial in 7 study subjects (≥ 18 years of age) should be conducted to assess the devices safety for clinical application.

The novel interdisciplinary solution approach is based on the combination of individualized 3D modeling, viable autologous tissue (contrary to all other prosthetic heart valves on the market), and preservation of the regenerative capacity of the valve replacement by maintaining the vitality of heart valve cells and tissue through the application of a novel crosslinker in the tissue preparation process. The GrOwnValve prothesis has the potential to be the first durable and regenerative heart valve for adults. Fabrication is performed on-demand in the operating room. The trial should be the first clinical investigation assessing this novel heart valve replacement approach. We are aiming for the GrOwnValve to be the standard of care, replacing current solutions.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years,
2. Intact appropriate tissue (preferably: Pericardium for pericardiectomy via thoracoscopy or thoracotomy; other option fascia lata, rectus fascia, or diaphragm),
3. Any of the following by transthoracic echocardiography and/or Cardiac Magnet

Resonance Imaging:

* For patients in New York Heart Association (NYHA) Classification II, III, or IV: Moderate (3+) or severe (4+) pulmonary regurgitation AND/OR mean systolic gradient across PV or RVOT ≥ 35 mmHg
* For patients in NYHA Classification I: Severe (4+) pulmonary regurgitation with RV dilatation or dysfunction and/or mean PV or RVOT systolic gradient ≥ 40 mmHg
* Written informed consent provided by study subjects and/or their parents or legal guardians as approved and required by the respective institutional review board and agrees to its provisions, and obtained before any research related test is performed

Exclusion Criteria:

* Lack of pericardium, or other appropriate tissue
* Active endocarditis or myocarditis or within 3 months before the screening date
* Patient or guardian unwilling or unable to provide written informed consent or comply with follow-up requirements
* Obstruction of the central veins (including the superior and inferior vena cava, bilateral iliac veins) such that the ensemble delivery system cannot be advanced to the heart via a transvenous approach from either femoral vein or internal jugular
* Pre-existing mechanical heart valve in any position
* Requires emergency surgery
* Need for concomitant additional mitral and tricuspid valves surgery
* Recipient of transplanted organs or currently an organ transplant candidate
* Pulmonary hypertension
* Connective tissue disorders
* Coronary artery disease
* Immunosuppressive disease
* Estimated survival less than 6 months
* Fertile females unable to take adequate contraceptive precautions, pregnant, or are currently breastfeeding an infant
* Acute myocardial infarction within 30 days to the screening date
* Stroke confirmed by CT, cerebrovascular accident (CVA), or transient ischemic attack (TIA) within 6 months before the screening date
* Hemodynamic or respiratory instability requiring inotropic or/and mechanical circulatory support, or mechanical ventilation within 30 days before the screening date
* Severe left ventricular systolic dysfunction with ejection fraction ≤ 20% or evidence of an intra-cardiac mass, thrombus, or vegetation assessed by echocardiography before the screening date
* Renal insufficiency with creatinine level 2.5 mg/dl within 60 days before the screening date
* Leukopenia with WBC \<3.5 x 109/L anemia with Hgb \<10 g/dl, or thrombocytopenia with platelet count \<50x103/l accompanied by a history of bleeding diathesis or coagulopathy within 60 days before the screening date
* Adult subject is an illicit drug user, alcohol abuser, prisoner, untreated psychiatry (limited compliance), or unable to give informed consent Clinical Research \| ECS - full application \| Application template \| CR.2-A2 \|Mar. 2021 3/25
* Major or progressive non-cardiac disease (liver failure, renal failure, cancer)that has a life expectancy of less than one year
* Inability to comply with all of the study procedures and follow-up visits
* Patients requiring pre-stenting for dilatation
* RV outflow greater than 30mm or that a 30mm stent can be used

Primary outcomes:
measure: Death
timeFrame: Up to 5 Years Follow-Up
measure: Major bleeding
timeFrame: Up to 1 Year Follow-Up
measure: Reoperation
timeFrame: Up to 5 Years Follow-Up
measure: Acute device-related complications
timeFrame: Up to 5 Years Follow-Up
measure: Oxygen supply
timeFrame: Up to 5 Years Follow-Up
measure: Valve opening and closure behavior
timeFrame: Up to 5 Years Follow-Up
measure: Valve closure behavior
timeFrame: Up to 5 Years Follow-Up
measure: Heart rhythm
timeFrame: Up to 5 Years Follow-Up
measure: Position and condition of the stent and structures
timeFrame: Up to 1 Year Follow-Up
measure: Blood flow
timeFrame: Up to 1 Year Follow-Up
Secondary outcomes:
measure: Availability of pericardium or other tissue for preparation of autologous pulmonary valve graft
timeFrame: Procedure (intra-operatively)
measure: Post-procedure length of stay
timeFrame: Up to day of discharge ( ≤ 30 days)
measure: Ventilation time
timeFrame: Procedure (intra-operatively)
measure: Freedom from conduction disturbances and arrhythmias need for permanent pacemaker implantation
timeFrame: Up to 3 months Follow-Up
measure: (Re-)Hospitalization
timeFrame: Up to 60 months (5 years) Follow-Up
measure: Comparison of pericardiectomy (if applicable) via thoracoscopy vs. thoracotomy
timeFrame: Procedure (intra-operatively)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Deutsches Herzzentrum der Charité
Study officials:
affiliation: Charité UNiveristätsmedizin Berlin, Deutsches Herzzentreum der Charité
name: Boris Schmitt, Dr.
role: STUDY_DIRECTOR
References: