Feasibility Study to Evaluate the Safety of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve

Pulmonary Valve Insufficiency Clinical Trial

— GECT  

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]

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05809856
• Other study ID #: 100592731
• Status: Recruiting
• Phase: N/A
• Start date: December 18, 2023
• Est. completion date: December 31, 2029

Study information

• Verified date: January 2024
• Source: Charite University, Berlin, Germany
• Contact: Boris Schmitt, Dr.
• Phone: +49 30 4593 2846
• Email: boris.schmitt[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7
• Est. completion date: December 31, 2029
• Est. primary completion date: January 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Pulmonary Valve Insufficiency

Intervention

Device:
• GrOwnValve - novel heart valve replacement approach
The autologous GrOwnValve is implanted into a stent before it is implanted via minimal-invasive transcatheter technique into the patients with high-grade pulmonary valve insufficiency and right ventricular dilatation. Control intervention/Reference test: Since the study is designed for investigating the safety of the procedure, there will not be a control group. However, the outcomes will be compared as a non-inferiority analysis with the standard of current medical care (Edwards SAPIEN 3 or Medtronic's Melody, both bioprosthetic transcatheter pulmonary valves).

Locations

Country	Name	City	State
Germany	Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Deutsches Herzzentrum der Charité	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	(valve-related, sudden, cardiac, and all-cause death)	Up to 5 Years Follow-Up
Primary	Major bleeding	Assessment if device-related major bleeding has occured by laboratory + echo + CT	Up to 1 Year Follow-Up
Primary	Reoperation	Questioning if device-related re-operation occured	Up to 5 Years Follow-Up
Primary	Acute device-related complications	Measurement tool: Spiroergometry; o Parameters: cardiac rhythm, load duration, reason for termination, Heart rate at rest, blood pressure, maximum load level, VE/VCO2, PetCO2, VE/VCO2 slope, VO2, Respiratory rate, VD/VT, SpO2, RER, Borg score, FEV1, FVC	Up to 5 Years Follow-Up
Primary	Oxygen supply	Measurement tool: Spiroergometry Parameters: cardiac rhythm, load duration, reason for termination, Heart rate at rest, blood pressure, maximum load level, VE/VCO2, PetCO2, VE/VCO2 slope, VO2, Respiratory rate, VD/VT, SpO2, RER, Borg score, FEV1, FVC	Up to 5 Years Follow-Up
Primary	Valve opening and closure behavior	Measurement tool: Echocardiography + Magnetic resonance imaging Parameter: 1.) blood flow velocity / stenosis, 2.) stiff leaflet, 3.) valve opening area Decision rule: blood flow velocity >4 m/s, abnormal or no leaflet motion when compared to neighboring leaflets, > 0.70 for 17 diameter, > 0.85 for 19, > 1.05 for 21, > 1.25 for 23, > 1.45 for 25, > 1.70 for 27, 1.95 for 29, and 2.25 for 31 mm annulus diameter	Up to 5 Years Follow-Up
Primary	Valve closure behavior	Measurement tool: Echocardiography + Magnetic resonance imaging Parameter: 1.) vena contracta, 2.) Proximal Isovelocity Surface Area (PISA) radius, 3.) Effective regurgitation orifice area (EROA=2p*r2*Va/Vmax), (iv) sagging leaflet Decision rule: 1.) less than or equal to 15% of the diameter of PA/stent at a Nyquist limit of 0.5-0.6 m/s, frame rate >20/sec, gain adjusted, sector small, 2.) equal or minor to 4 mm at a Nyquist limit of 0.2-0.4 m/s, frame rate >20/sec, gain adjusted, variance off, sector small, 3.) < or equal to 3% of the total cross-sectional area of the valve, 4.) n.a	Up to 5 Years Follow-Up
Primary	Heart rhythm	Assessment if new or higher grade of cardiac arrhythmia occured, i.e. newly ventricular extra systoly	Up to 5 Years Follow-Up
Primary	Position and condition of the stent and structures	Measurement tool: Echocardiography + Magnetic resonance imaging + computed tomography Parameter: 1.) GrOwnValve annulus, 2.) no broken struts of the valve stent Decision rule: 1.) +/- 1.5 mm from the native pulmonary valve annulus, 2.) n.a.	Up to 1 Year Follow-Up
Primary	Blood flow	Assessment of backflow and volume of blood by echo + MRI	Up to 1 Year Follow-Up
Secondary	Availability of pericardium or other tissue for preparation of autologous pulmonary valve graft	Visual assessment of pericardium	Procedure (intra-operatively)
Secondary	Post-procedure length of stay	Post-procedure hospital stay in days.	Up to day of discharge ( = 30 days)
Secondary	Ventilation time	Timepoints: Procedure Assessment: How long was the ventilation time for each patient within the allocation?	Procedure (intra-operatively)
Secondary	Freedom from conduction disturbances and arrhythmias need for permanent pacemaker implantation	Timepoints: Procedure + Discharge + Visit 1 Assessment: Is the implantation of a permanent pacemaker necessary due to disturbances or arrhythmias?	Up to 3 months Follow-Up
Secondary	(Re-)Hospitalization	Timepoints: Discharge, Visit 1, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6, Visit 7, Visit 8 Assessment: Is a (Re-)Hospitalization necessary due to procedure- or device-related complications?	Up to 60 months (5 years) Follow-Up
Secondary	Comparison of pericardiectomy (if applicable) via thoracoscopy vs. thoracotomy	Timepoints: Procedure Assessment: How was the pericardiectomy conducted, via thoracoscopy or thoracotomy	Procedure (intra-operatively)