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

A First-in-Human Feasibility Study to Evaluate the Safety (and Short Term Effectiveness) of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve [GECT]

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Valve Insufficiency
• Intervention / Treatment: Device: GrOwnValve - novel heart valve replacement approach

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.

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Boris Schmitt, Dr.; Phone Number: +49 30 4593 2846; Email: boris.schmitt@charite.de
• Study Contact Backup: Name: Frank Edelmann, Prof. Dr.; Phone Number: +49 30 450 553731; Email: frank.edelmann@charite.de

Study Locations

• Germany
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Recruiting
      • Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Deutsches Herzzentrum der Charité
      • Contact: Svenja Broschag, MSc; Email: svenja.broschag@dhzc-charite.de
      • Contact: Marvin Steitz, MSc; Email: marvin.steitz@dhzc-charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Sufficient appropriate tissue (preferably: Pericardium for pericardiectomy via thoracoscopy or thoracotomy, or sternotomy; other options are fascia lata, rectus fascia, peritoneum 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
   • Right ventricular ejection fraction (RV-EF): <40%.
   • Right ventricular end-diastolic volume (RVEDV): >150 ml/m2 (body surface area)
4. Written informed consent provided by study subjects obtained before any research-related test is performed

Exclusion Criteria:

• Active endocarditis or myocarditis or within 3 months before the screening date
• Patients 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, and bilateral iliac veins) such that the Ensemble-delivery system/ Performer™ - Guiding Sheath/ Extra Large Check-Flo® or GORE® DrySeal Flex + Ballon-in-Ballon-catheter cannot be advanced to the heart via a transvenous approach from either femoral vein or internal jugular
• Requires emergency surgery
• Recipient of transplanted organs or currently an organ transplant candidate
• Pulmonary hypertension
• Connective tissue disorders
• Coronary artery disease
• Immunosuppressive disease
• Estimated survival of less than 6 months
• Fertile females unable to take adequate contraceptive precautions (PEARL- Index < 1%)
• Females who are pregnant, or are currently breastfeeding an infant
• Acute myocardial infarction within 30 days of 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, or unable to give informed consent
• Subject is institutionalized by court order or by order of authority (e.g. prisoner, untreated psychiatry; limited compliance)
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer)that has a life expectancy of less than six months Inability to comply with all of the study procedures and follow-up visits
• Subjects who are dependent on the sponsor or investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Implantation of autologous GrOwnValve; Implantation of autologous GrOwnValve via minimal-invasive transcatheter technique into patients with high-grade pulmonary valve insufficiency and right ventricular dilatation.

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	(valve-related, sudden, cardiac, and all-cause death)	Up to 5 Years Follow-Up
Major bleeding	Assessment if device-related major bleeding has occured by laboratory + echo + CT	Up to 1 Year Follow-Up
Reoperation	Questioning if device-related re-operation occured	Up to 5 Years Follow-Up
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
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
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
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=2π*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
Heart rhythm	Assessment if new or higher grade of cardiac arrhythmia occured, i.e. newly ventricular extra systoly	Up to 5 Years Follow-Up
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
Blood flow	Assessment of backflow and volume of blood by echo + MRI	Up to 1 Year Follow-Up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Availability of pericardium or other tissue for preparation of autologous pulmonary valve graft	Visual assessment of pericardium	Procedure (intra-operatively)
Post-procedure length of stay	Post-procedure hospital stay in days.	Up to day of discharge ( ≤ 30 days)
Ventilation time	Timepoints: Procedure Assessment: How long was the ventilation time for each patient within the allocation?	Procedure (intra-operatively)
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
(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
Comparison of pericardiectomy (if applicable) via thoracoscopy vs. thoracotomy	Timepoints: Procedure Assessment: How was the pericardiectomy conducted, via thoracoscopy or thoracotomy	Procedure (intra-operatively)
Procedure-related death, major bleeding, reoperation, and other complications.	Assessment of the GrOwnValve procedure's safety. Therefore, procedure-related death, major bleeding, reoperation, and other complications will be documented combined and individually for 6 months. Whenever the procedure evaluates as "not safe", the reasons will be documented.	Follow-Up for 6 months

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: GrOwnValve GmbH
• Investigators: Study Director: Boris Schmitt, Dr., Charité UNiveristätsmedizin Berlin, Deutsches Herzzentreum der Charité

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Estimated): January 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 12, 2023

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Pulmonary Valve; Congenital Heart Diseases; Transcatheter Valve; Heart Valve Replacement; Medical Need; Durable; One-time-solution; Autologous Living Tissue
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Defects, Congenital; Pulmonary Valve Insufficiency
• Other Study ID Numbers: 100592731

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No