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FP7

ESPOIR Sintesi della relazione

Project ID: 278453
Finanziato nell'ambito di: FP7-HEALTH
Paese: Germany

Periodic Report Summary 1 - ESPOIR (European clinical study for the application of regenerative heart valves)

Project Context and Objectives:

Beginning in January 2012, the European Union started funding the European Clinical Study for the Application of Regenerative Heart Valves (www.ESPOIR-clinicaltrial.eu), coordinated by the Hannover Medical School, Germany, with a grant of 5.2 Million Euros for a period of four years. The aim of ESPOIR is to transplant a tissue-engineered human heart valve (decellularised homograft) which is tolerated by a patient’s immune system, lasts a lifetime and, for children, even holds the potential to grow with the patient.
The current gold standard for the treatment of certain heart conditions is the transplantation of mechanical or biological heart valves. However, both of these approaches also hold significant disadvantages. Mechanical valves require lifetime treatment to thin the patient’s blood, which can be dangerous for children or pregnant women. For this reason, clinicians often prefer to use biological heart valves from humans or animals. However, these valves also degenerate within eight to ten years, rendering a further transplantation necessary. Each reoperation entails a higher risk for the patient and the mortality risk increases in proportion to the number of reoperations. To address this problem, the ESPOIR consortium will test an innovative new approach using decellularised heart valves.
Decellularised heart valves are human donated heart valves which are treated by the company Corlife in a special laboratory to remove all biological material from the homograft, leaving a collagen matrix. These homografts have already been successfully transplanted in more than hundred paediatric and adolescent patients with promising results. So far, none of the transplanted decellularised valves has been rejected by the patients’ immune systems and none of the patients treated has required a reoperation. The ESPOIR consortium hopes to confirm these preliminary results within the four-year trial.
The ESPOIR consortium comprises eight leading European paediatric cardiac surgical centres (Paris-Hospital Necker, London-Great Ormond Street Hospital, Leiden-LUMC, Padua University, Zürich-Children`s Hospital, UZ Leuven, Chisinau-University Hospital, Hannover Medical School), two tissue banks, the German Society for Tissue Transplantation (DGFG) and the European Homograft bank who will provide the heart valves, and the innovative small enterprise Corlife, who will process the donated valves. Project management for the study is organized by the Leibniz University Hannover. Two hundred patients will take part in the trial which already shows significant potential for the future of heart valve transplantation.

Project Results:
Within the first reporting period a robust governance structure for the ESPOIR project (www.espoir-clinicaltrial.eu) was established including the implementation of an external Ethics and Governance Council (www.espoir-egc.eu ) to provide independent supervision and advice for the whole project.
The involved tissue banks have defined quality standards and standard operating procedures for the European-wide procurement of fresh, non-cryopreserved homografts and initiated intensified collaboration of tissue banks within Europe to establish strong procurement networks to ensure availability of decellularised heart valves for patients. Heart valves will only be distributed by non-for-profit tissue banks.
The involved company Corlife has built certified state-of-the-art clean-room facilities for processing of the heart valves and established detailed standard operation procedures. Formal approval of decellularised heart valves by the European authorities has been initiated by Corlife and is expected to be completed soon. During the process of formal approval, the ESPOIR consortium has already been able to make a contribution to standards and regulatory issues, as it was not clear whether these valves should be classified as a medicinal product or a medicinal drug. ESPOIR thereby has set an example for approval of similar regenerative medical products in the field of cardiovascular tissue engineering and through the clinical trial, will be able to disseminate this information.
The ESPOIR consortium has implemented advanced database infrastructure to provide long-term data on the overall performance of the transplanted heart valves. In addition the ESPOIR Registry was created which will also contain data of all decellularised heart valves transplanted before and outside the clinical trial. So far, the ESPOIR Registry contains data on 78 pulmonary valve and 29 aortic valve implantations in children, adolescents and adults.
The prospective trial on decellularised homografts will start shortly after final official approval of the study valve by the competent authorities in Europe.

Potential Impact:
5 million people with congenital heart defects live in the EU today. The life expectancy of affected patients has increased significantly in the last decades. Many congenital heart defects are directly related to heart valve disease leading to the need for valve replacement in many patients at young years. Age-related degeneration of heart valve cusps and leaflets also leads to increased prevalence of heart valve disease after the age of 60. As aortic valve replacement is the most frequently performed valve operation, a reduced reoperation rate would have relevant impact on direct and indirect health costs. If the mean time to reoperation, which is currently 8-10 years for biological prostheses, could be expanded by the use of decellularised heart valves at least to 15-20 years, the reoperation rate would be cut by half. As nearly every 10th heart valve operation is a ‘redo’ operation, this would lead to enormous direct cost reduction given the high numbers of heart valve operations in the EU (60,000 per yr., EACTS-database).
A lowered reoperation rate would also reduce the risk for heart failure as the myocardium is not exposed to pressure and/or volume overload by degeneration of biological valve prostheses and thereby limit health costs for the treatment of congestive heart failure.
In conclusion, as the number of humans with congenital heart defects is growing and the population in the EU is ageing in general, thereby leading to higher health costs, a reduction of costs for heart valve replacement could compensate for this to some extent.
Decellularised homograft valves also represent a good example for an evolving regenerative medicinal product which requires a standardized evaluation of quality, safety and efficacy. As there are only limited experiences in new regenerative medical therapies or devices so far it is important to broaden the experience in this rapidly developing area of medicine. ESPOIR will realise a large-scale trial which will also be the benchmark for further trials in regenerative medicine by its European wide multi-centre approach.
Ethical issues, especially important in the evolving field of regenerative medicine, will be directly addressed within ESPOIR via the Ethics and Governance Council. Clear and transparent information on these aspects will be made available via the project website to minimize patient concerns and to raise awareness among the general public throughout Europe regarding the importance of tissue donation, in line with the aims of the EU Tissue Directive (2004/23/EC).
As the proposed project will include pediatric patients in the clinical trials, it also aims to provide a best-practice example for this aspect. Future clinical trials in regenerative medicine for the benefit of children will have the opportunity to refer to the experience of ESPOIR with respect to ethics and European regulatory affairs (see on-going EU-Project RESPECT: Relating Expectations and needs to the Participation and Empowerment of children in Clinical Trials -http://www.patientneeds.eu).

List of Websites:

www.espoir-clinicaltrial.eu

Informazioni correlate

Contatto

Frank Dittrich
Tel.: +49 511 532 5343
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Life Sciences