Agency: European Commission | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.4.2-2 | Award Amount: 12.67M | Year: 2011
Paediatric drugs (PD) lack appropriate testing. Most drugs have inadequate information about dosing regimen, dose adjustment and how to administer them. These are longstanding problems that unquestionably require concerted efforts at the international level. Both the US and the EU have introduced paediatric legislation that facilitates participation of children in research and pharmaceutical innovation but initiatives are not always coordinated and often different approaches are used to deal with the same problems. The main aim of GRiP will be to implement an infrastructure matrix to stimulate and facilitate the development and safe use of medicine in children. This implementation entails active coordination of knowledge management efforts and integrated use of existing research capacity, whilst reducing the fragmentation and duplication of activities. The consortium will primarily focus on: 1) development of a Paediatric Clinical Pharmacology Training Program; 2) Validation and harmonisation of research tools specific for paediatrics; 3) Sharing of strategies and plans; 4) Use of ongoing/planned research studies to evaluate the feasibility of proposed research tools and strategies. GRiP brings together an exceptional range of high quality leaders and stakeholders that are very active in the context of EU and US paediatric medicines research. GRiP will mobilize 21 institutions as partners and at least another 16 major networks that represent several hundreds of clinical sites and a total of more than 1000 researchers across Europe, the US and Asia. The integration of the WHO, EMA and the NIH-NICHD associated networks, including the FDA, will be a major asset not just for an effective implementation of the network activities without duplication, but also for the rapid translation of GRiP deliverables into practice. This partnership will work closely with families to provide children with safe and effective medicines.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-1 | Award Amount: 7.63M | Year: 2011
-thalassaemia major is one of the most severe forms of chronic congenital anaemia. The recommended treatment consists in regular blood transfusions combined with chelating therapy to remove harmful iron accumulation in the body. The use of deferoxamine, the first chelating agent only available for subcutaneous administration is limited due to toxicity and the lack of compliance, despite its satisfactory therapeutic effects. An oral iron chelating agent, deferiprone, was authorised in Europe in August 1999 and recommended for the treatment of iron overload in patients with thalassaemia major when deferoxamine is contraindicated or inadequate. Despite a wide experience of the administration of deferiprone for thalassaemic patients, limited data are available on its use in children below 10 years and the need for additional data in this age subset was clearly indicated in the 2009 priority list approved by the Paediatric Committee at the European Medicines Agency (PDCO). In addition, according to the recent scientific advancements and in consideration of the anticipated benefit of this chelator in controlling cardiac iron overload, studies evaluating the effects of the deferiprone in all the paediatric ages and in all transfusion-dependent chronic congenital anaemia (including Sickle Cell Diseases) were also considered a critical therapeutic need. The DEEP project, in line with these premises, has been funded with the specific aim to produce a new oral liquid formulation of deferiprone suitable for the paediatric use and to provide evidences for the use of this chelator as first line therapy in the whole paediatric population (from 1 month to 18 years) affected by transfusion-dependent chronic anaemia. The condition under study in the DEEP project is rare. This poses special difficulties in the conduct of the studies due to the small patient population and the need to involve a large number of recruiting centres . However, being dedicated to develop an orphan drug, DEEP has been also recognised in the context of IRDiRC, the International Rare Diseases Research Consortium devoted to repurpose/develop 200 new drugs for Rare Diseases by the end of 2020. Main features of the DEEP project are: -The innovative design of the clinical studies including pharmacokinetic modelling for the definition of the most appropriate dosage of deferiprone in younger children, the cardiac MRI T2* evaluation as primary endpoint, a three years safety study aimed at evaluating deferiprone, in monotherapy or in combination, in the real worlds setting and, for the first time, a comparative efficacy-safety trial to compare the two existing oral chelators: deferiprone and deferasirox. -The DEEP Consortium including European and non-European Countries from the Mediterranean region where the transfusion-dependent congenital anaemia, in particular -thalassemia major, is particularly widespread: the collaboration within a multinational and multicultural network makes the Project extremely challenging due to many different ethical, methodological and social approaches to be explored and positively addressed.
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: HEALTH-2007-4.1-4 | Award Amount: 560.14K | Year: 2008
There are two objectives for this project, firstly to clarify the expectations and needs of children and their families who have participated or who might participate in clinical trials for new drugs in Europe. Secondly, to identify methods by which the expectations and needs can be translated into empowering and motivating participants in future clinical trails research. This will be achieved in three stages. The partners will be from different areas involving patients, clinicians, regulators, and researchers (industrial and academic) on a broad basis in order to cover a broad spectrum of diseases. Stage 1) The project will construct a basis for coordination and harmonization. This will involve a literature search and a preliminary workshop. We will build a web site for communication within the project and with a wider audience. Stage 2) We will ground our diverse experience and knowledge through benchmarking good practice case studies, and collecting opinions from patients organisations in Europe. The results will be presented at an expert harmonization workshop composed of all partners of the project. This workshop will identify the operating procedures needed to encourage empowerment and increase motivation for participation in clinical trials. Stage 3) The results of the project will be presented in a series of European conferences. This will ensure that the impact on clinical practice will be facilitated. This will help to improve translational research which depends upon the clinical trial process being undertaken with large enough populations to ensure safety of new products. Greater participation in clinical trials research will result in more valid and reliable products available for children as envisaged by the EC 1901/2006 Paediatric Regulation. In addition it will make European health businesses more competitive and will improve the global health in Europe.
Agency: European Commission | 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.
Agency: European Commission | 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: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2014 | Award Amount: 4.95M | Year: 2015
65,000 aortic valve replacements (AVR) are performed in Europe each year to treat acquired and congenital aortic valve diseases. In affected patients, mortality without AVR is extremely high and 50 % die within 2 years. Current AVR options are, however, limited for young patients - especially female patients - and those unwilling to accept life-long medical anticoagulation with its inherent risks. None of the currently available prostheses for AVR is tailored toward the individual patient or allows for individual regeneration. The ARISE project will bridge this therapeutic gap in a Phase II clinical study to determine the feasibility, safety and efficacy of regenerative heart valves for aortic valve replacement. After extensive preclinical work, Haverich et al. have used decellularized allogenic heart valve matrices for AVR on the basis of compassionate use in 34 patients with tentative assessment showing auspicious initial clinical results. However, transferring this regenerative approach to routine clinical application necessitates controlled prospective clinical trials which are lacking to date. The translation of research in regenerative medicine from bench to bedside is frequently hampered by lengthy and complex regulatory procedures. This holds especially true for regenerative solutions based on human cell or tissue products where regulatory paths at national level are often unclear. Making these products available across Europe adds a further level of complexity as regenerative products are not subject to harmonized procedures, such as those for pharmaceutical products within Europe. The ARISE consortium will address these challenges, integrating a network of six leading centres for cardio-thoracic surgery, each with proven track records in clinical research, an innovative SME experienced in bringing human tissue products to the clinic and market and expertise in ethical and regulatory aspects of regenerative medicine. .
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 11 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.
Agency: European Commission | 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.
Agency: European Commission | 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: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-2 | Award Amount: 7.95M | Year: 2013
TRANSLINK is a project devoted to assessing the mid-to long-term risk factors and improve the outcome of animal (bovine/porcine)-derived Bioprosthetic Heart Valve (BHV) implants. 300,000 patients/year benefit from BHV, a major healthcare problem (second most frequent cardiac surgery). BHV clinical outcome suffers from late dysfunctions restricting their application to older recipients. Based on a retrospective (already computerised) and prospective cohort of approximately 3,000 BHV recipients and control patients from 3 large EU cardiac surgery groups, TRANSLINK aims primarily to establish the possible role of recipients immune response (IR) against BHV as a major cause to mid- to-long term clinical dysfunction. Precise molecular analysis of preimplantation BVH sugar moieties will be performed. Possible indirect side-effects on BHV endocarditis and host vessels inflammation are secondary end points. Serial and trans-sectional blood samples will be dispatched to a battery of highly specialised partner groups for testing anti-Gal, -Neu5Gc and -hyaluronic acid antibodies (Ig) using both validated and newly designed screening tools, glycan array patterns, and macrophages/NK responses. Data will be crossed with clinical outcome scores. Project design aims at delivering comprehensive recommendations in the time-frame of the grant. Fundamental basic science progress in the field of carbohydrate antigens is also expected. Furthermore, prevention (BHV from engineered animal source lacking major antigens) and treatment (bioabsorbants of deleterious Ig) oriented remedies as well as prospective biomarkers of longterm BHV deterioration will be set up by three first-class SMEs. TRANSLINK may strongly impact the treatment of heart valve diseases by improving morbid-mortality in patients with heart valves diseases and increasing the indication of BHV to younger patients.