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Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-1 | Award Amount: 6.65M | Year: 2012

Acquired and congenital heart disease can necessitate heart valve replacement. However, current heart valve substitutes are not considered ideal as they need anticoagulation, bearing the risk of bleeding when manufactured from non-organic material, or they degenerate when they derive from animals or human tissue donators (homografts) thereby leading to frequent reoperation especially in the young population. An ideal heart valve substitute would overcome these limitations and even have the potential to grow when implanted in pediatric patients. Haverich et al. have developed an implant for heart valves, which is better tolerated than the known alternatives and which has the potential for regeneration by autologous recellularization. Implants derive from donated homografts, which are chemically treated to inactivate potential microorganisms and viruses. The heart valves then are decellularized chemically, so that only connective tissue remains, the matrix of the decellularized heart valve (DHV). DHV has been examined in extensive animal studies, including immunological and toxicological analysis, long term and growth models, all of which have shown that the implant is well tolerated and spontaneously recellularized by the recipient. The proposed ESPOIR project is based on auspicious early clinical results in 45 children and young adults. In order to drive translation of this promising regenerative approach towards practical clinical use and to reduce the burden of congenital heart defects in particular, the ESPOIR consortium will undertake a prospective multi-centre trial to include at least 200 patients from 8 leading European Centres for Congenital Heart Surgery, for robust statistical evaluation of DHV in direct comparison to conventional heart valve substitutes.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-4.2-2 | Award Amount: 3.77M | Year: 2008

The Safety Of non-Steroidal anti-inflammatory drugs (SOS) proposal aims to assess the relative cardiovascular (CVD) and gastrointestinal (GI) safety of non-steroidal anti-inflammatory drugs (NSAIDs). The NSAIDs are divided in traditional NSAIDs (tNSAIDs) and the newer COX-II inhibitors(coxibs). The aim will be fulfilled by a two-phase approach comprising systematic reviews and synthesis of CVD and GI risk information from clinical trials and published observational studies, followed by the design and conduct of a multi-country study in existing health care databases in the UK, Netherlands, Germany and France, comprising medical information on at least 35 million persons. A data ware house will be constructed that will contain all pre-specified and locally elaborated anonimized data from inception cohorts of NSAID users. Data elaboration is standardized through a common protocol that will be designed on the basis of information and knowledge gaps observed in the systematic literature reviews, plus information requirements for the statistical and decision models. The database study will yield risk estimates for CVD and GI bleeding for each individual NSAID by dose and duration and by other important effect modifiers (e.g. aspirin use). Separate models will be built for children since the indications and dosages differ and little is known on the safety of NSAIDs in this group as they are often prescribed off-label. Special emphasis will be put on the assessment and evaluation of methodological issues, such as confounding by indication, and outcome validity as these constitute the most important threats to the interpretation, robustness and perceived validity of observational studies. The results of the literature reviews, analysis of observational databases and re-analysis of published studies will feed into a decision model for clinicians to support treatment decisions and a decision model for regulatory authorities that will focus on the public health risk.

Colombo A.,San Raffaele Scientific Institute | Chieffo A.,San Raffaele Scientific Institute | Frasheri A.,ASL Trapani P.O. | Garbo R.,San Giovanni Bosco Hospital | And 12 more authors.
Journal of the American College of Cardiology | Year: 2014

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) following second-generation drug-eluting stent (DES) implantation is still debated. OBJECTIVES The aim of this study was to test the noninferiority of 6 versus 12 months of DAPT in patients undergoing percutaneous coronary intervention with second-generation DES. METHODS: The SECURITY (Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy) trial was a 1:1 randomized, multicenter, international, investigator-driven, noninferiority study conducted from July 2009 to June 2014. Patients with a stable or unstable angina diagnosis or documented silent ischemia undergoing revascularization with at least 1 second-generation DES were eligible. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 12 months. The main secondary endpoint was a composite of cardiac death, MI, stroke, definite or probable stent thrombosis, or BARC type 2, 3, or 5 bleeding at 12 and 24 months. RESULTS: Overall, 1,399 patients were enrolled in the study and randomized to receive 6 months (n = 682) versus 12 months (n = 717) DAPT. The primary composite endpoint occurred, respectively, in 4.5% versus 3.7% (risk difference 0.8%; 95% confidence interval [CI]: -2.4% to 1.7%; p = 0.469) at 12 months. The upper 95% CI limit was lower than the pre-set margin of 2%, confirming the noninferiority hypothesis (p < 0.05). Moreover, no differences were observed in the occurrence of the secondary endpoint at 12 months (5.3% vs. 4.0%, difference: 1.2%; 95% CI: -1.0 to 3.4; p = 0.273) and between 12 and 24 months (1.5% vs. 2.2%, difference: -0.7%; 95% CI: -2.1 to 0.6; p = 0.289). Finally, no differences were observed in de finite or probable stent thrombosis at 12 months (0.3% vs. 0.4%; difference: -0.1%; 95% CI: -0.7 to 0.4; p = 0.694) and between 12 and 24 months of follow-up (0.1% vs. 0%; difference: 0.1%; 95% CI: -0.1 to 0.4; p = 0.305). CONCLUSIONS: In a low-risk population, the noninferiority hypothesis of 6 vs. 12 months DAPT following secondgeneration DES implantation appears accepted for the incidence of cardiac death, MI, stroke, de finite/probable stent thrombosis, and BARC type 3 or 5 bleeding at 12 months. (Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy; NCT00944333). © 2014 by the American College of Cardiology Foundation. Source

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 8.19M | Year: 2016

Liver cancer in the paediatric population is rare with an incidence approximately 1-1.5 per million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project relates to topic PHC 18 establishing effectiveness of health care interventions in the paediatric population. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research programme linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial - PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo has the best surgical operation (surgical resection or liver transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally, we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-4.2-1 | Award Amount: 2.58M | Year: 2009

Cancer chemotherapy has a key role in the successful treatment of a number of childhood cancers. Nevertheless, at least 20% of patients are not cured by current therapies and a significant number experience debilitating toxicities. Given the high cure rates and potential life-span of survivors of childhood cancer, it is particularly important to minimize the impact of potential chronic toxicities. For several of the most widely-used drugs, little is known about their pharmacokinetics and metabolism in children, particularly very young children (<3 years). There are many examples where such knowledge has been used to optimize the use of chemotherapeutic drugs, both to avoid toxicity and to maximize the therapeutic effect. The need for further research to investigate these drugs in children is acknowledged in the Priority List for Studies into Paediatric Medicinal Products, issued by the EMEA. Doxorubicin is on this list and is one of the most important drugs used in the treatment of childhood cancers. Several national groups have been successful in studying the pharmacology of drugs used in paediatric oncology. However, in order to recruit sufficient patient numbers for meaningful studies it is necessary to establish a wider group, bringing together the successful elements of established national organizations. The EPOC group combines leading pharmacologists, paediatric oncologists, regulatory organizations and a management structure which will successfully deliver data of appropriate quality on which to base future clinical use of this drug and to meet the demands of the EMEA priority list. Such data will form the basis of future applications for Paediatric Usage Marketing Authorization for doxorubicin. The overall aim of the consortium is to provide data that will guide the optimal use of this drug in the clinic, and also meet the regulatory requirements of the EMA.

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