Trial Portfolio

By combining the expertise, resources and capacities of national networks, ECRIN promotes synergistic, multinational clinical trials. Summaries of current and past trials in the ECRIN portfolio are shown below.
Full title
Autologous Adipose-Derived Mesenchymal Stromal Cells in the Treatment of Mild to Moderate Osteoarthritis
Summary
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.
Full title
Taxonomy of Neurodegenerative Diseases: Observational Study in Alzheimer's Disease and Parkinson's Disease
Summary
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.
Full title
ALdosterone antagonist Chronic HEModialysis Interventional Survival Trial
Summary
This study is designed to establish the effects of spironolactone in comparison to placebo on the composite endpoint of nonfatal Myocardial Infarction (MI) and acute coronary syndrome, hospitalization for heart failure, nonfatal stroke or cardiovascular-induced death. The primary endpoint will be the time to onset of the first incident.
Full title
A multi-centre randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on the progression of left ventricular mass and diastolic function in patients with structural heart disease
Summary
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.
Full title
Clinical Trial for the Regeneration of Cartilage Lesions in the Knee (NosetoKnee2)
Summary
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).
Full title
Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease: Comparative Effectiveness Research of Existing Technologies
Summary
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.
Full title
The EUropean TRAnsplantation and INnovation (EU-TRAIN) consortium for improving diagnosis and risk stratification in kidney transplant patients
Summary
The EU-TRAIN project was formed by gathering reference kidney transplant centres in a fully operating European network including 12 partners. Our ambitious but realistic goals are: to provide clinicians with innovative and accessible tools for early prediction of individual risk of allograft rejection and transplant loss; to personalise clinical management and treatment and; to improve allograft outcomes.
This project will engineer a risk stratification system applied to kidney transplant patients by analysing the integration of several layers of data (clinical, histological, immunological data as well as gene expression and novel biomarkers) - the TRAnsplant Comprehensive Evaluator of Risk (EU-TRACER). EU-TRACER will be generated and validated in two dedicated studies including a randomised control trial.
Full title
Conservative Iron Chelation as a Disease-Modifying Strategy in Parkinson's Disease
Summary
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.
Full title
Hydroxycholoroquine in paediatric ILD_START randomized controlled in-parallel group, then switch to placebo active drug, and STOP randomized controlled in-parallel group to evaluate the efficacy and safety of hydroxychloroquine (HCQ)
Summary
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.
Full title
A phase I/IIa, randomized study to evaluate the safety and the effectiveness of a Combination of Therapeutic Vaccine, the Broadly Neutralizing Antibody and 10-1074 and the Latency Reversing Agent Romidepsin to Achieve a Functional Cure of HIV in chronical
Summary
9/03/2018
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.
Full title
Immunome project consortium for AutoInflammatory Disorders
Summary
ImmunAID is seeking to enable a rapid and accurate diagnosis across all the spectrum of SAID, in order to improve clinical management of SAID patients, through a graded approach:
- Identification and validation of novel Omics- and pathway-based diagnostic biomarkers, with a strong link to pathogenic pathways involved in autoinflammation, and likely to be considered as genuine “autoinflammation signatures”;
- Development of a robust clinical decision algorithm to assist physicians, having a progressive and targeted approach (triage process) when facing a patient with suspected SAID, and thus avoiding the prescription of a large number of costly and frequently inadequate diagnostic investigations in parallel;

The ImmunAID research will likely lead to the reorganization of SAID into a new comprehensive and pathogenesis-driven classification with strong clinical impact.
Summary
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 aim of the LIVERHOPE SAFETY trial is to assess the safety and tolerability of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis.
The aim of LIVERHOPE EFFICACY is to assess the efficacy of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis to prevent ACLF development.
Full title
Dry age-related macular degeneration: Development of novel clinical endpoints for clinical trials with a regulatory and patient access intention
Summary
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.
Full title
Antibodies against Nogo-A to enhance plasticity, regeneration and functional recovery after acute spinal cord injury, a multicenter international randomized double-blinded placebo-controlled Phase II clinical proof
Summary
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).
Full title
A multi-centre, open-label, randomized, comparative clinical trial of two different doses of bone marrow autologous human mesenchymal stem cells plus biomaterial versus iliac crest autologous graft, for bone healing in non-union after long bone fractures
Summary
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).
Full title
Oxytocin Treatment in neonates and infants (BaBies) with Prader-Willi syndrome: effects of intranasal administrations of oxytocin in infants aged from 0 to 3 months vs. placebo on sucking and swallowing (phase III clinical trial)
Summary
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).
Full title
Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging with ‘Minimally-Invasive Segmental Artery Coil-Embolization’: A Randomized Controlled Multicentre Trial
Summary
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.
Full title
Prophylactic oropharyngeal surfactant for preterm infants: a randomised trial
Summary
Premature babies are at high-risk of respiratory failure due to respiratory distress syndrome (RDS). Surfactant given into the trachea is an effective treatment for infants who are intubated for RDS. Endotracheal intubation is difficult and is associated with adverse effects. A strategy of supporting premature newborns with continuous positive airway pressure (CPAP) and reserving intubation and surfactant for those who develop respiratory failure despite CPAP yields better results than intubating all infants for surfactant. However, nearly half of infants managed with CPAP are ultimately intubated for surfactant.
We will establish whether giving preterm infants surfactant into their oropharynx at birth, with the intention that they aspirate it, reduces the rate of intubation in the first 5 days of life.Infants born before 29 weeks gestation will be eligible for inclusion in this multi-centre randomised trial. Written informed consent will be obtained before delivery. Infants will be randomly assigned to receive oropharyngeal surfactant immediately at birth in addition to CPAP or standard care with CPAP alone. Caregivers will not be masked to group assignment.
Randomisation will be stratified by centre and gestation at birth (<26 weeks; 26-28 weeks). Primary outcome of the study is intubation for respiratory failure in the first 120 hours of life. Enrolled infants will be intubated for persistent apnoea and/or bradycardia in the delivery room (DR), or for respiratory failure in the neonatal intensive care unit (NICU) defined as ≥ 2 of worsening clinical signs; acidosis; oxygenation – FiO2 > 0.4; hypercarbia; or apnoea treated with mask ventilation. To demonstrate a reduction in the rate of the primary outcome from 48% in the control group to 26% with oropharyngeal surfactant with 80% power and a = 0.05, we need to recruit 250 infants. Adverse events will be recorded and measure secondary outcomes of clinical interest (rate of DR intubation; duration of ventilation and respiratory support; rate of bronchopulmonary dysplasia at day 28 and chronic lung disease at 36 weeks’ corrected age; mortality before hospital discharge). All outcomes will be determined at or before hospital discharge; this duration will vary according to clinical course [e.g. for 1 day (for participants who die shortly after enrolment) to several months]. Poractant alpha (Curosurf, Chiesi Farmeceutici, Parma, Italy) is a natural surfactant prepared from porcine lungs. It is approved for endotracheal use for prevention and/or treatment of RDS in premature infants. It is currently not licensed for oropharyngeal administration, therefore we will examine the off-label use of a licensed product. It is a randomised, parallel group, controlled Phase III trial.
Full title
Prevention of Complications to Improve Outcome in Elderly Patients with Acute Stroke
Summary
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.
Full title
Penumbral Rescue by Normobaric O=O Administration in Patients With Ischaemic Stroke and Target Mismatch ProFile: A Phase II Proof-of-Concept Trial
Summary
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.
Full title
Optimizing response to Li treatment through personalized evaluation of individuals with bipolar I disorder: the R-LiNK initiative
Summary
The objective of this study is to identify the eligibility criteria for treatment with Li in BDI in terms of response, safety and tolerability.
Full title
REgenerative therapy of intervertebral disc: a double blind phase 2b trial of intradiscal injection of mesenchymal stromal cells in degenerative disc disease of the lomber SPINE unresponsive to conventional therapy
Summary
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.
Full title
A Randomized Multicenter Clinical Trial in Patients with Subjective Cognitive Decline At Risk for Alzheimer's Disease to Assess the Short-term Effects of a Standardized Meditation Intervention vs. Active Control on Behavioral Measures
Summary
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.
Full title
An Open Innovation testing bed for the development of high-risk medical devices
Summary
The aim of TB-MED is to establish an open innovation testing bed (TB) specialized in the development of high-risk devices (Class III). In 2015, 11% of new medical devices (MDs) receiving CE Mark were Class III devices. However, according the new regulation on MD high risk devices will require stricter ex-ante control via a new pre-market scrutiny mechanism, and additional supervision by the Medical Device Coordination Group. TB-MED will provide an integral service to accelerate the development of medical devices reducing time to market, covering technology development from TRL4 to TRL7 and business management services.

Based on a Quality by Design (QbD) concept TB-MED will generate robust scientific knowledge that will promote the development of MDs emphasizing product understanding.
Full title
Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window
Summary
TENSION is a prospective, open label, blinded endpoint (PROBE), European two-arm, randomized, controlled, post-market study to compare the safety and effectiveness of endovascular thrombectomy as compared to best medical care alone in the treatment of acute ischemic stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early CT Score (ASPECTS) score of 3-5 and in an extended time window (up to 12 hours or unknown time of symptom onset). Up to 714 subjects will be randomized. Primary endpoint will be functional outcome assessed by the modified Rankin scale at 90 days post-stroke ("mRS shift analysis"). By this, TENSION will provide evidence of efficacy and safety of thrombectomy in an acute stroke population with uncertain benefit of endovascular stroke treatment.
Full title
Multi-center, randomized, double-blinded study of Teriflunomide® in radiologically isolated syndrome (RIS)
Summary
Purpose: To prospectively study the efficacy of Teriflunomide in extending the time to a seminal acute or progressive demyelinating event in a cohort of RIS subjects.
Rationale: RIS subjects are frequently exposed to disease modifying therapies despite the lack of scientific literature supporting the use of such treatments. Earlier treatment intervention may extend the time to the first acute or progressive clinical event resulting from CNS demyelination and reduce radiological progression. In addition, early treatment may result in more profound effects on reducing disability progression long-term.
Primary outcome: The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination.
Population: This study will include RIS subjects from the Europe who fulfill 2009 RIS Criteria.
Full title
Walking Easier with cerebral palsy
Summary
Cerebral palsy (CP) results from a lesion to the brain that occurs before or around birth, and it is the most common cause of physical disability in childhood. Approximately 70% of children with CP are able to walk, but experience varying degrees of restrictions related to this function. In children with CP, walking speed is reduced, balance is impaired and energy cost during walking is increased. Consequently, children with CP are less active and restricted in social participation compared to their peers. During the last two decades, targeted muscular injections of botulinum toxin A (BoNT-A) have become the standard treatment to reduce spasticity with the intention to make walking easier in order to facilitate the children's activity level and participation. Treatment with BoNT-A is mainly offered to children. Already at the age of 6 years, approximately 60% of the Norwegian children with CP have been treated with BoNT-A; mainly in the lower limbs. The evidence for a functional effect is surprisingly limited, despite the fact that this drug has been used for 20 years. The drug is expensive not only in terms of drug expenses, but also personal costs as well as the costs for the patients and their families. The objective of the study is to evaluate whether injections of BoNT-A in the calf muscles (mm.gastrocnemius and soleus) make walking easier in children/adolescents with CP within a time span of 6 months, and to evaluate whether an improvement in energy cost during walking is associated with increased daily activity, increased walking capacity, less pain and perceived improved performance and satisfaction. It is a double blinded placebo controlled randomized parallel-group design Phase IV study. This study cordinated by Professor Torstein Vik and sponsored by St. Olavs University Hospital, Trondheim Norway. Study will be conducted in three european countries (Norway, Poland and France).

Past Studies

Full title
Scandinavian Starch for Severe Sepsis/Septic Shock Trial
Summary
Fluid is the mainstay treatment in sepsis resuscitation, but the effects of different crystalloid and colloid solutions on outcome remain unknown.

Previously, a high molecular weight hydroxyethyl starch, HES 200, was used, but this was found to cause acute kidney failure in patients with severe sepsis. As kidney failure is an independent risk factor for death in these patients, HES 200 is not used anymore. In stead a lower molecular weight starch, HES 130, has been developed. Presently, this is the preferred colloid in Scandinavian intensive care units (ICU), but the effects of HES 130 in ICU patients are currently unknown. The proposed Scandinavian multicentre study will be conducted to assess if HES 130 contributes to acute kidney failure in patients with severe sepsis. As HES 130 is widely used, the trial will provide important safety data to clinicians who resuscitate septic patients.
Full title
Biomarker Evaluation in Advanced Stage Cervical Cancer by an International Working Group. Tumor Stages (1B1 - 4)
Summary
Prospective Multicentric European trial for Cervical cancer, not previously treated, with tumour biopsies, and blood collection for molecular analysis at predetermined time points.
Full title
Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers (CaPP3 Israel)
Summary
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).
Full title
First Adult Safety Trial on Nasal Live Attenuated B. Pertussis Vaccine
Summary
The purpose of this study is to evaluate the safety and immunogenicity of a new live attenuated vaccine against whooping-cough. It is a phase1, single centre, dose-escalating, placebo-controlled study on a genetically modified B. pertussis strain given as a single intranasal dose to healthy adult male volunteers.

Effective vaccines are needed to protect young infants (from 0 to 6 months, today the most vulnerable age group), preferably after a single administration very early in life. The successful outcome of this project would constitute an important milestone towards nasal vaccination of infants, possibly at birth with a novel, single-dose pertussis vaccine. Our ultimate aim is to protect infants in the most vulnerable age group, before the regular vaccination schedule using already available vaccines is applied. The ultimate aim is thus not to replace current vaccination schedules with available vaccines, but to add a first nasal vaccination to protect very early in life.
Full title
Efficacy of FOLFOX Alone, FOLFOX Plus Bevacizumab and FOLFOX Plus Panitumumab in Patients With Resectable Liver Metastases (BOS2)
Summary
Patients presenting with multiple innumerable liver metastases will probably never come to resection, however, for all others, including patients with numerous multiple metastases or large metastases,resection should be considered after limited chemotherapy.
There is consensus for a backbone chemotherapy consisting of fluoropyrimidine + oxaliplatin. FOLFOX was used in the previous EORTC study and is again recommended.

The addition of targeted agents to standard chemotherapy in the perioperative strategy for mCRC might increase the ORR and R0 resectability, without significant increase in toxicity, therefore translating to a better outcome.
It was therefore decided to design an open label, randomized, multi-center, 3-arm late phase II study.
Arm A: (standard) mFOLFOX6 + Surgery Arm B: (experimental) mFOLFOX6 + Bevacizumab + Surgery Arm C: (experimental) mFOLFOX6 + Panitumumab + Surgery
Full title
Efficacy Study of Antimicrobial Catheters to Avoid Urinary Infections in Spinal Cord Injured Patients
Summary
Antiseptic Silver Alloy-Coated Silicone Urinary Catheters seems to be a promising intervention to reduce urinary tract infections; however, research evidence cannot be extrapolated to spinal cord injured patients.
The study is an open, randomized, multicentric, and parallel clinical trial with blinded assessment. The study includes spinal cord injured patients who require at least seven days of urethral catheterization as a method of bladder voiding. Participants are on-line centrally randomized and allocated to one of the two interventions (Antiseptic Urinary Catheters or Conventional Catheters). Catheters are used for a maximum period of 30 days or removed earlier at the clinician criteria.
The main outcome is the incidence of urinary tract infections by the time of catheter removal or at day 30 after catheterization, the event that occurs first. Intention-to-treat analysis will be performed, as well as a primary analysis of all patients.
The aim of this study is to assess whether silver alloy-coated silicone urinary catheters reduce urinary infections in spinal cord injured patients.
Full title
Efficacy Study of IgY (Antibody Against Pseudomonas) in Cystic Fibrosis Patients
Summary
The purpose of this study is to prolong the time to reinfection with Pseudomonas aeruginosa after successfully treated acute or intermittent infection.
Full title
Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis
Summary
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)
Full title
Multimodal Intervention for Cachexia in Advanced Cancer Patients Undergoing Chemotherapy
Summary
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.
Full title
Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia: A Randomized, Controlled Trial (POEM rcpmt)
Summary
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.
Full title
PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
Summary
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.
Full title
A Randomized European trial of Steroids versus Clobazam Usage for Encephalopathy with Electrical Status Epilepticus in Sleep
Summary
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.
Full title
Staphylococcus Aureus Bacteremia Antibiotic Treatment Options
Summary
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.
Full title
Safeguarding the Brain of Our Smallest Children - an Investigator-initiated Randomised, Blinded, Multinational, Phase II Feasibility CT on Near-infrared Spectroscopy Monitoring Combined With Defined Treatment Guidelines Vs. Std. Monitoring...
Summary
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.
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Secondary Prevention of Cardiovascular Disease in the Elderly Trial
Summary
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.
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Multiple Versus Single Dose of Ivermectin for the Treatment of Strongyloidiasis
Summary
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.
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Fluconazole Versus Micafungin in Neonates with Suspected or Culture-Proven Candidiasis
Summary
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.
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Treat Infection in NeoNates 2
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The aim of the TINN2 study is to evaluate the efficacy of azithromycin in prevention of bronchopulmonary dysplasia in preterm neonates.
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A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
Summary
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.
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Transfusion Requirements in Septic Shock
Summary
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.
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Target Temperature Management After Cardiac Arrest
Summary
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 33°C and 36°C for 24 hours after cardiac arrest?
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A Phase IIb Randomized, Double-blind, Parallel Placebo- and Active-controlled Study to Assess the Efficacy and Safety of VBP15 in Ambulatory Boys with Duchenne Muscular Dystrophy (DMD)
Summary
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).