Work plan / packages

Overall strategy of the work plan 

Early clinical results of decellularized heart valves (DHV) for pulmonary heart valve replacement (PVR) are extremely encouraging: DHV show superior performance compared to established valve prostheses and, most importantly, have the potential to grow. The aim of this Clinical Trial is to validate these hypotheses in a sufficiently large patient cohort to enable robust statistical comparison with established cohorts , who have been treated with other prostheses for pulmonary valve replacement (PVR). 

Project Phase 1
Regulatory Approval & Establishment of Management Structures (M1 – 6)

All approval procedures and production facilities will be finalized and ready-to-run before the start of the project. Phase 1 of the project will focus on the establishment of robust structures to underpin effective project and quality management, decision-making, and accountability throughout the duration of the project and beyond. This will include the convening of the Steering Committee and the external Ethics and Governance Council to monitor and advise project activities throughout the project lifetime. Furthermore, a framework for the effective dissemination and use of knowledge generated by the project will be established to ensure maximum impact of the project in all phases. 

Project Phase 2
Procurement and Processing (M 1 – 30)

Procurement of homografts for the clinical trial will be coordinated by the European Homograft Bank (EHB, Partner 11). This is a prerequisite for the decellularization process, which will be managed by Corlife GbR (Partner 9). Sufficient homograft resources will be guaranteed via the EHB, with an annual production of 300 homografts, and the Deutsche Gesellschaft für Gewebetransplantation (DGFG, Partner 10), with an annual production of 50 homografts. Moreover, we will initiate and support additional local procurement of homograft valves from explanted hearts during heart transplantation, by so called “domino-transplantation”, to facilitate procurement of small homograft sizes. 

Project Phase 3
Clinical Trial (M7 – 42)

A prospective multi-centre trial at 8 leading centres in the field of congenital heart disease in Europe will be performed to evaluate DHV for PVR. The proposed recruitment of 25 patients from each of these clinical centres within 24 months is realistic given the number of PVRs performed in these institutions every year. Furthermore, it is anticipated that patient demand will increase, as there already exists a large waiting list at the MHH (Partner 1) for potential decellularized homograft recipients. The calculated cohort size of 200 patients will allow a thorough evaluation of re-intervention rates, hemodynamical performance and durability of DHV for PVR in congenital heart disease. Also, growth potential of these regenerative heart valves will be assessed.

Project Phase 4
Analysis, Follow-Up and Sustainability Measures (M43 – 48) 

Statistical analysis in direct comparison to current valve substitutes will allow for exact scientific evaluation of DHV. Results will be published and disseminated to the scientific community, patient organisations and political stakeholders. Furthermore, measures to support follow up beyond the time frame of ESPOIR will be implemented to assess long term durability of DHV. Established structures for homograft procurement within the framework will be used for further exploitation of the developed method of decellularization. Strategic partnerships may be used for technology transfer to consortium partners and other institutions in the EU.