Every year, 1.3 million Europeans have a stroke and one million ultimately die of stroke. One third of stroke patients remain dependent on the help of others. The annual costs for stroke care in Europe are estimated at € 64.1 billion. Stroke incidence increases almost exponentially with age, and the personal, societal, and economic burden of stroke is therefore largely driven by its frequent occurrence in the elderly. The elderly have been strongly underrepresented in previous stroke trials and treatment guidelines have no recommendations specific to this important group. Elderly patients are at the highest risk of complications after stroke, such as infections, fever, and dysphagia. These complications are strongly and independently associated with a higher risk of death or dependency. We will perform a pragmatic, randomised, open clinical trial with blinded outcome assessment in 3800 patients with acute stroke aged 66 years or older, to assess whether pharmacological prevention of infections and fever, and early management of dysphagia, will reduce the risk of death, poor functional outcome, and poor quality of life, and lead to reductions in the costs of stroke care throughout Europe. Patients will be randomised using a factorial design to preventive treatment for 4 days with ceftriaxone, paracetamol, and/or metoclopramide, or to ‘standard care’ alone. The primary outcome is functional outcome at 3 months, assessed with the modified Rankin Scale (mRS), and analysed with ordinal logistic regression. The study will have 90% power to detect a statistically significant shift towards a favourable outcome, assuming a 5% absolute increase in the proportion of patients with a good outcome (mRS 0 to 2) in the intervention group, compared with controls. This simple, safe, and generally available treatment strategy has the potential to lead to an annual reduction of over 25 000 elderly Europeans being dead or dependent as a result of stroke, at very low costs.

Experts in virology, immunology and clinical hepatitis B patient care with an excellent research and translational track record in hepatitis B virus (HBV)-host interaction form the interdisciplinary TherVacB consortium. They jointly tackle the major challenges in HBV therapy – the virus’s resistance to cure. TherVacB aims at breaking immune tolerance in chronic HBV infection and achieving HBV cure. Occurrence of neutralizing antibodies and HBV-specific T cell responses characterize spontaneous resolution of HBV infection that are lacking in chronic infection. We will use our IP-protected heterologous prime-boost therapeutic vaccination scheme with proven efficacy in preclinical models of hepatitis B to target and activate B and T cell responses. Two protein prime injections with clinically approved, adjuvanted particulate HBV S and core protein antigens shall induce neutralizing antibodies and prime T cells that are boosted with an MVA vector expressing HBV core, S, L and polymerase antigens covering >95% of HBV found worldwide. Having secured significant funding and partnerships to obtain GMP-produced vaccine components and to prepare a first-in-human application, TherVacB aims at a clinical proof-of-concept of the therapeutic hepatitis B vaccine in patients with chronic hepatitis B. The consortium will establish a patient registry and perform a multi-center phase Ib/IIa clinical trial that aims at proving safety of the therapeutic vaccine and inducing immune control of chronic HBV infection. One study arm will be realized in Tanzania to build up local capacity, because Africa carries a large burden of HBV infection but lacks diagnostic and therapeutic options. An innovative immune monitoring will quantify HBV-specific immunity and define novel biomarkers to predict treatment response. Finally an ethical and an empirical study will evaluate the recruitment of patients by social media which is very effective for infectious diseases that tend to stigmatize patients