A phase IIb, prospective, multicentre, double-blind, triplearm, randomized versus placebo trial, to assess the efficacy of a single injection of either 2 or 10 x 106 autologous adipose derived mesenchymal stromal cells (ASC) in the treatment of mild to moderate osteoarthritis (OA) of the knee, active and unresponsive to conservative therapy for at least 12 months.
This study aims to validate the mechanism-based taxonomies of Alzheimer's Disease and Parkinson's Disease generated by the AETIONOMY Innovative Medicines Initiative (IMI) project for two biomarkers for Alzheimer's Disease and two biomarkers for Parkinson's Disease.
Prospective, randomized, placebo-controlled, multi-centric international phase IIb clinical trial. The target population consists of patients with cardiac structural remodelling with or without symptoms of heart failure (maximum NYHA II). The objective is to evaluate mirabegron (a new β3-specific agonist) over 12 months as add-on to standard treatment compared to standard treatment alone. Endpoints focus on cardiac remodelling: Quantitative indices of hypertrophy and left ventricle (LV) function, in addition exercise tolerance is investigated.
Cervical cancer is the second most common cause of cancer death in women worldwide. There is a need for improvement in diagnosis and treatment. The aim of the BIO-RAIDs study is to identify predictive biomarkers of standard treatment response using an integrative approach combining exome sequencing, proteomics and tumor micro environment analyses.
The purpose of this study is to investigate the efficacy of an engineered cartilage transplant (N-TEC) in comparison to a cell-activated matrix (N-CAM) for the treatment of articular cartilage lesions in the knee. The main innovations in this trial are the use of nasal chondrocytes and the implantation of a tissue in contrast to cells seeded on a matrix. The goals of the trial are to: (i) evaluate whether implantation of a more mature graft (tissue therapy) is beneficial for the quality and durability of the repair tissue and the clinical outcome, (ii) determine the potential of the mature graft to integrate with the adjacent cartilage and form hyaline repair tissue and (iii) assess the efficacy of each treatment in correlation to the characteristics of the defect (e.g. acute versus chronic setting).
This is a pragmatic randomised controlled trial (PRCT) evaluating the superiority of CT over ICA concerning effectiveness in stable chest pain patients with intermediate pretest probability of coronary artery disease.
The purpose of this study is to determine if systemic cooling to a target temperature of 34 to 35°C, started within six hours of symptom onset and maintained for 24 hours, improves functional outcome at three months in patients with acute ischaemic stroke.
This study evaluates the effect of iron chelation as a therapeutic strategy to slow the progression of Parkinson's disease. Half of participants will receive the deferiprone to 15 mg / kg twice daily morning and evening (30mg / kg per day), while the other half will receive a placebo. The treatment lasts nine months.
The surfactant dysfunction disorders are an important group of molecularly and histologically defined entities, belonging to the interstitial lung diseases in children (chILD). Mutations in genes encoding for surfactant protein C, surfactant protein B, the lipid transporter ABCA3, thyroid transcription factor 1 and others, cause a significant group of phenotypically similar chronic interstitial lung diseases with high morbidity and early mortality.
Unfortunately no successfully proven treatments are available. Beyond oxygen supplementation, nutritional support and immunizations, the small molecule hydroxychloroquine (HCQ) has been identified during decades of trial and error treatments for surfactant dysfunction disorders. Together with promising in vitro data, HCQ has the potential as an innovative lead compound for this group of diseases.
During a previous FP7 project ending 2016 the highest priority for further study in clinical trials was assigned to HCQ due to greatest patients´ needs, wide off-label usage, the results of a worldwide Delphi process and direct recommendation from the Committee for Orphan Medicinal Products (COMP) members. As part of that project the most suitable study design was developed.
This randomized phase 2b double blind clinical study of HCQ in patients with surfactant dysfunction disorders has a design which allows a flexible beginning, either the initiation or the withdrawal of HCQ. The primary objective is to investigate if HCQ improves the oxygenation compared to placebo in a group of 60 well defined subjects with surfactant dysfunction disorders. Secondary objectives of the project will generate important knowledge on patient reported outcomes, health economics and other parameters.
Build on a large body of preparatory work we have assembled a team of experienced collaborators from Austria, Germany, Italy, Poland, Portugal, Spain and Turkey and their linked European Clinical Research Infrastructure Network (ECRIN) to successfully achieve the goal to repurpose HCQ for surfactant dysfunction disorders
The main goal of HIVACAR is to change the current paradigm of HIV treatment by obtaining a functional cure for HIV (i.e., control of viral load to levels below the threshold of 50 copies/ml and maintenance of high CD4+ T-cell count after discontinuation of antiretroviral therapy) thanks to effectively targeting residual virus replication and viral reservoirs. In order to do so, the planned novel strategy is to successfully combine immune-based therapies, including therapeutic vaccines and broadly neutralizing antibodies with latency reversing agents, in a proof-of-concept phase IIa clinical trial.
The HIVACAR project will lead to a reduction of the actual costs related to HIV treatment and management and of the social public health as well as an improvement in the patients’ quality of life. HIVACAR has been conceived under the framework of responsible research and innovation, so patients and other stakeholders will have a key role from the inception of the project until obtaining the results. Patients will be perfectly aware of how this therapy has been conceived and the real impact and change in their actual quality of life, as well as how the clinical trial has been designed and the consequences of participating in it. In addition, patients (and the general population) will tailor the project and its results dissemination and communication. This patient engagement will not be limited to the clinical trial but also to the rest of the activities of the project, so patients and the general society will be aware of how the research is developed and can include the patients’ point of view in the research activities. In addition, the socio-economic and psycho-social impact of the new treatment will be also analysed so overwhelming data on the benefits and impact of the new treatment will be obtained and shown to all stakeholders.
Webpage of the Project: http://www.hivacar.org/
The purpose of this study is to prolong the time to reinfection with Pseudomonas aeruginosa after successfully treated acute or intermittent infection.
The objective of the LIVERHOPE project is to evaluate a novel therapeutic strategy for patients with cirrhosis based on a combination of rifaximin and simvastatin, targeting the main pathophysiological mechanisms of disease progression , namely the impairment in the gut-liver axis and the persistent hepatic and systemic inflammatory response. This dual therapeutic approach is supported by preclinical data showing excellent and very promising results.
LIVERHOPE will include two randomized double-blind trials (LIVERHOPE SAFETY and LIVERSHOPE EFFICACY) to investigate safety, tolerability and efficacy of combination of simvastatin plus rifaximin in patients with decompensated cirrhosis in six EU countries (285 patients will be enrolled in two trials in Germany, France, Italy, Spain, The Netherlands, and the United Kingdom). The expected impact is to halt progression to acute-on-chronic liver failure, the main cause of death, to decrease complications of the disease, to reduce hospital re-admissions, to improve cost-effectiveness of therapy.
The major objective is to develop novel clinical endpoints for clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (iAMD). Additional objectives are to characterise visual impairment in iAMD and its progression, as well as identify risk factors for progression to late stage AMD.
Cancer cachexia is a multi-factorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. There is an urgency for improving management, but there is no consensus on the optimal treatment for cancer cachexia. Several single therapies for cancer cachexia have been examined in clinical trials, with disappointing overall results. As multiple factors are responsible for the development of cachexia, it has been argued that optimal cachexia interventions should target all components: multimodal therapy for a multimodal problem. The overall aim of this study is to early prevent the development of cachexia rather than treatment late in the disease trajectory. From a patient perspective a short term effect will be to improve physical and psychological function, to reduce symptom burden and to improve survival. In other words live a longer and better life during and after chemotherapy. Direct effects of the cachexia intervention are expected to be reduction of weight and muscle loss, and improved physical activity and quality of life.
Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The incidence of spinal cord injury is about newly injured 10’000 people per year in the EU, and due to an almost normal life expectancy more than 200’000 patients are living with a spinal cord injury in the EU. The impact on the individual quality of life is high, and social costs are enormous. Recent preclinical research in animal models succeeded to greatly enhance axonal sprouting, fiber regeneration and neuroplasticity following injuries of brain and spinal cord. These results warrant translation now to patients suffering from acute spinal cord injury. A previous phase I clinical study using intrathecal application of a nerve fiber growth promoting antibody against the growth inhibitory protein Nogo-A has shown in patients with complete spinal cord injury that this treatment is safe and well tolerated. The present study will enroll patients with various degrees of complete to incomplete acute spinal cord injury for a double-blind, placebo-controlled trial to test the efficacy of this antibody therapy to improve motor outcome and quality of life of tetraplegic patients. The enrollment of patients with different degrees of spinal cord injury is considered essential to reveal drug activity and eventual proof of concept in a broad patient population. Advancements in clinical trial design, improved prediction algorithms of clinical outcomes and development of surrogate markers (in cerebro-spinal fluid/serum and by neuroimaging) will allow for scrutinizing the effectiveness of this novel treatment in an unprecedented way. A positive outcome of this trial will represent a breakthrough for the future therapy of spinal cord injuries and beyond (traumatic brain injury, stroke, multiple sclerosis).
This clinical trial involves two comparative analyses:
- Comparison of efficacy in terms of superiority of hBM-MSCs + biomaterial (both experimental arms, low and high doses) versus iliac crest autologus graft (active comparator arm). The principal endpoint is bone consolidation at one year, defined as a combination of clinical and radiological improvements: radiological consolidation (considered as a new bone formation across the fracture site visible in 3/4 cortices, on at least 3/4 views, qualitative analysis) without pain (with and without weight bearing) and without further reoperation in the callus site.
- Comparison of efficacy in terms of non-inferiority (target delta of 0.10 points) of low dose hBM-MSC+Biomaterial versus high dose of hBM-MSC+Biomaterial. The principal endpoint is the radiological consolidation, measured in a scale from 0 to 1, considering the mean consolidation of 0.6875 points (quantitative analysis).
Prader-Willi syndrome (PWS) is a rare chronically debilitating and life-threatening disease without efficient treatment. It is a genetic neurodevelopmental disorder with neonatal poor feeding, requiring nasogastric tube feeding, and social skills followed by early onset of obesity, severe behavioural disturbances and comorbidities. Pre-clinical data supported the hypothesis that OXT rescues early phenotype and modifies the course of the disease via its potential neuromodulation effect, if administered in a post-natal short window of opportunity. This is a European phase III randomised double-blind placebo trial, already approved by EMA, evaluating the effects of early intranasal OXT in PWS neonates/infants. This trial is coordinated by Pr M Tauber (France) and sponsored by the Centre Hospitalier Universitaire de Toulouse will be conducted in 5 European countries (France, Belgium, Italy, Netherlands, and Germany).
PAPA-ARTIS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.
Achalasia is a rare esophageal disorder which is characterized by a loss of esophageal motoneurons and impaired gastrointestinal peristalsis and food transit. Peroral Endoscopic Myotomy (POEM) is a new endosurgical technique for achalasia in which a surgical myotomy is created using a flexible endoscope through the mouth, completely avoiding any skin incisions. The aim of this study is to compare short and long-term feasibility, safety and efficacy of endoscopic (POEM) with laparoscopic myotomy (Heller myotomy) in the treatment of achalasia.
Elderly patients have a high risk of complications after stroke, such as infections or fever. This study aims to assess whether preventive treatment in the first four days of hospitalisation with ceftriaxone, paracetamol, and/or metoclopramide prevents the most common complications and reduce the risk of death or long-term disability compared to standard care alone.
The PROOF project now seeks to demonstrate that NBHO (high-flow 100% oxygen at >45 L/min via a non-rebreather mask, or FiO2=1.0 for intubation/ventilation) reduces infarct growth from baseline to 24 hours compared to standard treatment if administered at 3 hours after onset of anterior circulation IS, in patients with proximal vessel occlusion and salvageable tissue at risk. The study is multi-center, adaptive phase-IIb, randomized, open-label with blinded-endpoint (PROBE design).
The primary efficacy criterion will be infarct growth from baseline to 24 hours. Secondary endpoints will be NIHSS 24h, categorical shift in the pre-stroke modified Rankin Score, QoL and cognition at day 90. Potential surrogate biomarkers, health economics and societal impacts will be assessed. If NBHO proves its neuroprotective potential in this selected population, phase-III trials in all IS patients may be undertaken. Considering its low costs and ease of use, NBHO may impact stroke care worldwide.
The aim of this study is to establish which treatment is best for children with Electrical Status Epilepticus in Sleep (ESES) syndrome, by treating 130 children with ESES syndrome with steroids (inflammation inhibitors) or clobazam and evaluating change in cognitive functioning after 6 and 18 months.
The primary outcome of this trial is to evaluate the effectiveness of intradiscal injection of bone marrow mesenchymal stromal/stem cells (BM-MSCs) in reducing chronic lower back pain (LBP) using the visual analog scale (VAS) and functional status (Oswestry scale) after 12 months of treatment, defining responders in case of at least 20% improvement in VAS or Oswestry scale at month 12 compared to a baseline with absolute change of 20 mm on a 100 mm scale.
In a multicenter, open-label, randomized controlled trial we aim to demonstrate that an early switch from intravenous to oral antimicrobial therapy is non-inferior to a conventional 14-days course of intravenous therapy regarding efficacy and safety. An early switch from intravenous to oral therapy would provide several benefits such as earlier discharge, fewer adverse reactions associated with intravenous therapy, increased quality of life, and cost savings.
As the number of older people in Europe grows, increasing healthy life years is a priority. Cognitive decline, dementia (e.g. Alzheimer’s disease, AD), sleep disturbances and depression, all related to psychological distress and anxiety, are significant drivers of reduced quality of life in older adults. This study is part of a project that builds on evidence that lifestyle factors and meditation practice have the potential to downregulate these adverse factors and positively impact mental and neurological conditions including AD. In particular, the study aims to assess the short-term effects of an eight-week meditation intervention (versus cognitive training) in patients with subjective cognitive decline at risk for AD on behavioural measures including anxiety and wellbeing.
The purpose of this study is to evaluate the efficacy of a polypill strategy containing aspirin (100 mg), ramipril (2.5, 5 or 10 mgs), and atorvastatin (40 mgs) compared with the standard of care (usual care according to the local clinical practices at each participating country) in secondary prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent revascularization) in elderly patients with a recent myocardial infarction.
Ivermectin is currently the best drug to cure strongyloidiasis, but the standard single dose of 200 mcg/kg is probably not enough to guarantee a cure. As strongyloidiasis can be fatal in immunosuppressed patients, it is mandatory to define the optimal dosage to eradicate the parasite. The aim of this study is to define the most effective dose schedule of ivermectin to cure strongyloidiasis.
Huntington's disease is an autosomal dominant disease characterised by movement disorders and cognitive and neuropsychiatric disturbances. The clinical features usually emerge between 30 and 50 years of age and there is currently no curative treatment. Brain energy deficiency plays an important role in the pathophysiology of the disease. This study asks whether the administration of triheptanoin can effectively improve Huntington's disease as assessed by MRI, in vivo spectroscopy and clinical evaluation.
VISION-DMD (Phase 2 Clinical Trials of VBP15: An Innovative Steroid-like Intervention on Duchenne Muscular Dystrophy, DMD) is a Phase 2a and 2b randomised, double-blind, parallel placebo- and active-controlled study. It will assess the safety and toxicity (phase 2a) and safety and efficacy (phase 2b) of the orphan drug VBP15 in ambulatory boys with Duchenne muscular dystrophy (DMD), a rare recessive X-linked form of muscular dystrophy. Funded by Horizon 2020 and the sponsor, Reveragen Biopharma Limited, the project aims to advance clinical development of VBP15 as a new therapy to revolutionise care for all patients with DMD by 2020. The study will be carried out over 18 to 24 months in approximately 15 countries and 30 international study sites. The phase 2a study will be conducted at approximately 10 U.S. study sites. The phase 2b study, supported by ECRIN, will be conducted at approximately 30 international study sites in 14 different countries (UK, France, Italy, Spain, Belgium, Netherlands, Denmark, Sweden, Switzerland, Poland, Czech Republic, Turkey, Israel, and Australia).
Intravenous hydroxyethyl starch (HES) is routinely used to stabilise patients with severe sepsis. Since high-molecular-weight HES may cause acute kidney failure in sepsis patients, it has been replaced by low-molecular-weight HES 130/0.4. What are the effects of HES 130/0.4 on mortality and endstage kidney failure in patients with severe sepsis?
A randomised double blind dose non-inferiority trial of a daily dose of 600mg versus 300mg versus 100mg of enteric coated aspirin as a cancer preventive in carriers of a germline pathological mismatch repair gene defect, Lynch Syndrome. Project 3 in the Cancer Prevention Programme (CaPP3).
Current pertussis (whooping cough) acellular vaccine strategies do not protect very young infants. Vaccination using a genetically modified B. pertussis strain administered nasally should mimic infection and induce strong immune responses, even in infants, without causing disease. Is this vaccine safe in humans and does it illicit sufficient immune response?
In patients with liver metastasis from colorectal cancer who will undergo liver surgery, perioperative chemotherapy using the drug combination FOLFOX is standard. This study aims to evaluate whether or not the addition of either Bevacizumab or Panitumumab to FOLFOX increase progression-free survival compared with FOLFOX alone?
The purpose of this trial is to make a comparison between the use of antiseptic silver alloy-coated silicone urinary catheters and the use of conventional silicone urinary catheters in spinal cord injured patients to prevent urinary infections.
Non-alcoholic fatty liver disease (NAFLD) is responsible for an increasing prevalence of liver disease and is becoming the commonest cause of liver disease in the western world. NAFLD is recognised to be the hepatic manifestation of the metabolic syndrome, which is a cluster of metabolic abnormalities characterised by abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. In its mildest form there is an accumulation of fat in the liver (steatosis) without any liver damage, however in many cases it progresses to non-alcoholic steatohepatitis (NASH), and cirrhosis. Current treatment options for NASH are limited in efficacy, necessitating the development of more effective options. New agents such as Glucagon-like Peptide-1 (GLP-1) agonists that improve diabetic control and facilitate weight loss have been suggested as therapies in NASH. No published studies to date have assessed the impact of the GLP-1 agonist, Liraglutide, on liver histology and metabolism in obese patients with NASH. This study hypothesises that treatment with liraglutide will result in a significant improvement in histological disease activity in overweight patients with NASH, in the presence or absence of Type 2 Diabetes (T2DM)
This is a multicentre European double-blind, randomized and controlled trial with 2 parallel groups (1 study medication, 1 placebo) in order to analyse the impact of ACE inhibitors (ACEi) in subjects who carry a mutation but have not yet developed DCM (dilated cardiomyopathy). Objective of the trial: Study the impact of ACE inhibitors (ACEi) in subjects who carry a mutation (leading to a genetic form of heart failure) but have not yet developed DCM.
The primary objective of the SafeBoosC trial is to examine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral NIRS oximetry and implementation of an rStO2-specific clinical treatment guideline. We hypothesise that by using the specified treatment guideline to respond to cerebral monitoring readings outside the target range, we would reduce the burden of hypo- and hyperoxia and consequently reduce brain injury.
This is an investigator-initiated randomised, blinded, multinational, phase II feasibility clinical trial involving preterm infants from 12 European countries.
This study is designed to determine whether micafungin is as efficacious as the current standard of fluconazole, to compare the safety of the two drugs in the treatment of proven neonatal candidiasis.
It is also designed to further elucidate the pharmacokinetics of the two products in the growing and developing neonate and premature infant.
The aim of the TINN2 study is to evaluate the efficacy of azithromycin in prevention of bronchopulmonary dysplasia in preterm neonates.
Patients with blood poisoning - sepsis - often receive blood transfusions in the intensive care unit. The evidence that blood transfusion leads to improved outcome is limited and the blood may be harmful to some of these patients. To bridge the gap between clinical practice and evidence, a large randomised clinical trial is needed to document the efficacy and safety of RBC transfusion in these very sick patients.
Therapeutic hypothermia is recommended for unconscious survivors of out-of-hospital cardiac arrest. Are there differences in mortality, neurological function and adverse events between a target temperature management at 33Â°C and 36Â°C for 24 hours after cardiac arrest?