Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-2 | Award Amount: 7.70M | Year: 2014
Coronary artery disease (CAD) is the leading cause of death in high-income countries. Invasive coronary angiography (ICA) is the reference standard for the diagnosis of CAD and allows immediate therapy. However, only 40% of patients undergoing ICA actually have obstructive CAD and ICA has relatively rare but considerable risks. Coronary computed tomography (CT) is the most accurate diagnostic test for CAD currently available. CT may become the most effective strategy to reduce the ca. 2 million annual negative ICAs in Europe by enabling early and safe discharge of the majority of patients with an intermediate risk of CAD. To evaluate this, we propose the DISCHARGE project that will be implemented by a multinational European consortium. The core of the project is the DISCHARGE pragmatic randomised controlled trial. The primary hypothesis will be that CT is superior to ICA for major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) after a maximum follow-up of 4 years in a selected broad population of stable chest pain patients with intermediate pretest likelihood of CAD. The trial will include 23 clinical sites from 18 European countries ensuring broad geographical representation. Comparative effectiveness research of complementing work packages include gender-related analysis, systematic review of evidence, cost-effectiveness analysis, and health-related quality of life. DISCHARGE has the capability to influence current standards and guidelines as well as coverage decisions and will raise awareness among patients, health care providers, and decision-makers in Europe about the effectiveness and cost-effectiveness of coronary CT angiography.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.4.2-1 | Award Amount: 14.96M | Year: 2012
The consortium led by UKER and EuroHYP, the European Stroke Research Network for Hypothermia, proposes a large, multicentre clinical trial which will assess mild hypothermia as a novel treatment for ischemic stroke. Stroke is the second cause of death world-wide and the second cause of lost disability-adjusted life years in high-income countries. Stroke incidence rises exponentially with age, so its social and economic burden will grow with the ageing of the European population. Current treatment options for the 80 to 85% of all strokes due to cerebral ischaemia - around. 900,000 events in Europe every year, or one every 40 seconds - are extremely limited. Systematic review of experimental studies suggests that hypothermia is the most promising intervention identified to date. Therapeutic cooling is effective in reducing ischaemic brain injury following cardiac arrest, and hypothermia is therefore considered by experts the most promising treatment for patients with acute ischaemic stroke, next to reperfusion strategies. The EuroHYP-1 trial is a pan-European, open, randomised, phase III clinical trial which will assess the benefit or harm of therapeutic cooling in 1500 awake adult patients with acute ischaemic stroke. In addition to efficacy and safety, the economic impact of therapeutic hypothermia will be assessed, along with several sub-studies involving imaging, ultrasound, and biomarker methods. The investigators involved in the EuroHYP-1 consortium are leading European experts in statistical design and analysis, therapeutic hypothermia, imaging, health economics, ultrasound, biomarkers, and trial execution (implementation and monitoring). Moreover in addition to these academic experts the consortium also involves European patient and family advocacy groups and small and medium-size enterprises, and the joint endeavours of this extended team will ensure the successful enrolment of patients at eighty hospitals across 25 countries in Europe.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: ICT-26-2014 | Award Amount: 3.39M | Year: 2015
The diagnosis and management of acute Sepsis is a critical area where fast and accurate results can translate into life changing health outcomes for individuals. The overall aim of RAIS is to develop a new point-of-care label-free microarray platform and validate it for quantifying levels of specific Sepsis biomarkers. The approach uses a novel interferometric technique ultimately capable of providing very large arrays of tests. Specific objectives and activities include: (i) an optical microarray reader based on a disruptive proprietary design combining interferometric lens-free microscopy and proximity CCD or CMOS image sensing; (ii) a microarray plate, in a proper microfluidic cartridge, consisting of a transparent slide with a novel nano-structured surface geometry to increase the detection sensitivity and covered by specific receptors to capture bio-markers; (iii) their integration in a portable and battery powered label free microarray platform potentially capable of measuring more than 1 million bio-targets simultaneously. The developed technology will be capable to detect micro-ribonucleic acids (microRNAs), interleukins and other specific proteins associated to Sepsis using a few microliters of blood or serum samples, in a concentration of a few pg/ml, within 30 minutes (sample to result) and at a cost per patient of less than 50. In this way, patients will be put on the right treatment more rapidly, potentially reducing the Sepsis mortality rate of more than 70%, with estimated cost savings of more than 10 billion per year as a consequence of shorter hospital stays, reduced use of unnecessary drugs and lower associated insurance bills. The technical approach, targeted device, application and the addressed market sector are perfectly in line with the call H2020-ICT-2014-1 - Photonics KET - Biophotonics for screening of diseases: Mobile, low-cost point-of-care screening devices for reliable, fast and non- or minimally-invasive detection of diseases.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-1 | Award Amount: 7.00M | Year: 2013
Fanconi anemia (FA) is a rare inherited syndrome characterized by the early development of bone marrow failure and increasing predisposition to cancer with age. Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for hematopoietic manifestations of FA, although associated with complications arising from myeloablation, graft versus host disease and increased incidence of squamous cell carcinoma. The genetic correction of autologous hematopoietic stem cells (HSC) with lentiviral vectors constitutes a recent and safe alternative for the treatment of different genetic diseases affecting mature cells from different tissues and/or committed progenitors of the hematopoietic system. One of the key features of FA that make it a unique disease for gene therapy approaches rely on the characteristic proliferation defect that is already evident in the very primitive HSCs. Thus, a marked survival advantage would be expected from corrected HSCs, potentially allowing normalization of hematopoiesis in the absence or after mild conditioning. Difficulties in the collection of sufficient numbers of HSC from FA patients and the use of sub-optimal transduction protocols with gammaretroviral vectors limited the success of FA gene therapy trials conducted 10 years ago in the USA. Our innovative approach to develop for the first time an efficient and safe gene therapy of FA is based on two recent innovations: 1) Discovery of potent HSC mobilizers, such as plerixafor, and 2) Development of a new lentiviral vector by members of this Consortium, designed as Orphan Drug by the EC in December 2010. The principal objective of this Project is, therefore, the development of a multicentric Phase I/II gene therapy trial for FA-A patients, based on the genetic correction of plerixafor\G-CSF mobilized HSCs with the novel lentiviral vector, accompanied by comprehensive and groundbreaking safety and efficacy patient monitoring studies.
BIO-DRIM - Personalized minimization of immunosuppression after solid organ transplantation by biomarker-driven stratification of patients to improve long-term outcome and health-economic data of transplantation
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-1 | Award Amount: 7.98M | Year: 2012
Organ transplantation has emerged as the gold standard therapy for end-stage organ failure. Incomplete control of chronic allograft injury but also the adverse effects of long-term immunosuppression (IS) continue to challenge the long-term success of transplantation. The paradigm is shifting from increasing net-IS by novel drugs to the concept of minimizing long-term IS as early as possible. However, data were almost completely generated by trial-and-error observational studies. It suggests an unmet need to stratify transplant (Tx) patients regarding their immunological responsiveness to the allograft and their respective individual need of IS. The central focus of the project is the implementation of biomarker-driven strategies for personalizing IS to improve the long-term outcome and to decrease the adverse effects and costs of chronic IS. This includes 5 innovative investigator-driven biomarker clinical trials designed by the consortium with >1800 (screening) / 1000 (trial) patients. The following issues will be addressed: -targeted complete/partial weaning of standard IS in long-term stable liver and kidney Tx patients identified as operationally tolerant by recently developed biomarker panels-prevention of CNI-based standard IS in low-responder kidney Tx recipients by perioperative biomarker-based stratification-shifting high to low-responder kidney Tx patients suitable for early minimisation by the recently explored selective targeting of alloreactive effector/memory T cells -implementing new biomarker candidates supporting personalized IS within the clinical trials-analysing the health-economic impact of biomarker-guided personalized IS -studying the mechanisms behind successful weaning (regulation/effector balance) -disseminating the results and developing commercialisation by partnering with SME/industry. The project will take advantage and exploit recent research findingsIndices of Tolerance (IOT) and RISET but also of other international groups.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-22-2016 | Award Amount: 6.92M | Year: 2016
ZIKAction proposes to set up a multidisciplinary research network across Latin America with a focus on maternal and child health to coordinate and implement urgent research against the current ZIKV outbreak and lay the foundation for a preparedness research network against future emerging severe infectious threats in these vulnerable populations. Our Consortium brings together Latin American and European leaders in paediatric infectious disease research, including virologists, epidemiologists, immunologists and obstetric, neonatal and paediatric practitioners, all with a wealth of experience in vertical transmission (VT) studies, a group uniquely placed to evaluate the potentially causative relationship between ZIKV and severe reported complications. ZIKAction will collect data from prospective cohorts of pregnant women and infants to assess ZIKV complications with the necessary level of evidence which is currently lacking. Complementary work in virology will take advantage of repeated biological samples from these cohorts, while pathogenesis studies on animal models will elucidate risk factors and mechanisms of VT. Partners experience in conducting trials among pregnant women and children and close contact with other relevant researchers will allow rapid launch of additional interventional studies, including the addition of sites and partners, to address remaining research gaps against ZIKV. Recognizing the breadth and complexity of the research questions presented by the current ZIKV epidemic and the potential for future severe emerging infectious threats, ZIKAction will actively seek out collaborations with relevant initiatives already existing or under development to maximize synergy and avoid duplication of efforts. Our focus on vertical transmission and maternal and child health would nicely complement a range of other activities including clinical and laboratory studies in the general population, surveillance, and work in public health and prevention.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 7.92M | Year: 2012
Glioblastoma (GBM) is a rare (2-3 incidences in 100,000) and fatal disease. Each year, approximately 13,000 new cases of GBM are diagnosed in Europe. The 5-year survival rate of this highly aggressive tumor entity under conventional therapy is less than 6%. Currently available therapeutic options neglect the individuality of each patients disease and only temporarily influence tumor progression with poor effect on overall survival. Introduction of novel highly innovative personalized approaches would have tremendous impacts for the life course of affected patients without additive toxicities. Active cancer immunotherapy aims to trigger the patients immune system, specifically cytotoxic T lymphocytes (CTLs) and T helper cells, to defend the body against the cancerous disease. The Glioma Actively Personalized Vaccine Consortium (GAPVAC) aims to conduct a highly innovative pioneering project with active personalized immunotherapy to improve patient treatment. In a Phase I/II study at the center of this proposal, glioblastoma patients will receive a fully personalized peptide-based vaccine as a result of full-genome sequencing and complete peptidomics analysis of the patients tumor. Thus, the latest developments in next-generation sequencing, proteomics, immunology, biomarker research and small-scale GMP peptide manufacturing will be uniquely combined to deliver the next generation of personalized medicine to cancer patients. GAPVACs goal is to test safety, feasibility and efficacy (biological and early clinical) of this totally novel, completely personalized approach of immunotherapy. GAPVAC is therefore specifically answering the call HEALTH.2012.1.2-1 Development of technologies with a view to patient group stratification for personalized medicine applications by a 4 years project.
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.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-06-2014 | Award Amount: 2.95M | Year: 2015
Chronic kidney disease (CKD) is an important public health problem worldwide, especially in older people. Indeed, population aging in industrialized countries is accompanied by an increase in the prevalence of CKD and its complications. Although its prevalence and the importance of an early diagnosis to prevent complications such as end-renal stage disease (ESRD), screening programme in Europe are highly heterogeneous, fragmented, being in most cases based on opportunistic rather than structured assessments of patients. The main objective of the SCOPE project is to evaluate a large scale screening programme for CKD in the older population (age 75\) in Europe. Specific objectives are (i) to assess existing methodologies to screen for CKD among older adults, including the use of Comprehensive Geriatric Assessments (CGA); (ii) to investigate innovative biomarkers potentially useful for CKD screening; (iii) to evaluate the cost-effectiveness of CKD screening in a population at high risk of kidney function decline and ESRD; (iv) to provide evidence for further development of European recommendations, as well as an education programme in this field. This will be achieved also thanks to the creation of a large observational database including a cohort of older people aged 75 years or more, enrolled within the framework of an observational, multinational, multicenter, prospective study with a 2-year follow up. The SCOPE database will include a CGA-based screening and a collection of biological samples at baseline and at regular intervals during the study. The SCOPE project will provide evidence for the increased use, or discontinuation of, existing screening and prevention programmes in the field of CKD, allowing informed decisions by policymakers. It will contribute to capacity building in the assessment of such screening and prevention programmes in an equitable and cost-effective manner, thus improving health outcomes in the older European population.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 5.06M | Year: 2013
FLUTCORE will develop a novel universal influenza A virus (IAV) vaccine based on the tandem core vaccine platform. Recent influenza pandemics have emphasized the urgent need for better vaccines that are reactive with multiple IAV subtypes and that are no longer dependent on intimate knowledge of the prevalent virus. We propose to replace the existing seasonal IAV vaccine with a virus like particle (VLP) carrying several invariant universal influenza antigens. Previous attempts to use these targets have failed due to the poor antigen expression and immunogenicity. The highly immunogenic tandem core system overcomes this limitation. Specifically, we propose to develop a VLP carrying two or more invariant influenza antigens, express these in yeast and then examine immunogenicity in mice. The vaccine will be further tested in the rigorous ferret system before being scaled up for manufacture. An optimal clone will then be transferred to an accredited contract manufacturer for production. A phase I clinical trial will be carried out once pre-clinical toxicology has been successfully completed. Our consortium will examine the immune responses in both animals and humans thoroughly to ensure that the vaccine candidate chosen can produce a protective IAV immune response in all individuals. To achieve these objectives, our proposal builds upon the complementary expertise of seven high-performing partners representing four European countries, with world leadership in HBV core biology, immunological analysis, commercial manufacture and influenza clinical trials, making our consortium ideally positioned to develop the vaccine and to take it from bench to bedside. The leading role of SMEs in the consortium will ensure that the technology developed by FLUTCORE will generate highly marketable products, offering both improved patient protection and long-term cost savings for health care in Europe once annual influenza vaccines are replaced.