CONTRAST 2.0

2023

Acute stroke management faces significant challenges despite recent progress. Intracerebral hemorrhage (ICH) accounts for 15% of all strokes and lacks effective treatment options. Additionally, only a small portion of acute ischemic stroke (AIS) patients qualify for intra-arterial therapy (IAT), and even after successful IAT, many experience poor outcomes due to incomplete microvascular reperfusio. The ambition of CONTRAST 2.0 is to improve outcome after stroke and increase the number of patients who are eligible for acute treatment. CONTRAST 2.0 addresses the aims of the Dutch Heart Foundation with an integrated research program to develop and evaluate new treatment strategies for AIS, ICH and Subarachnoid Hemorrhage (SAH) in preclinical studies, a series of complementary RCTs and registries. To establish an optimal setting for long-term preclinical studies on brain damage caused by ischemia-reperfusion or hemorrhage and the effects of neuroprotection, we will develop a platform for assorted translational studies in the most appropriate animal models with clinically relevant output parameters. As such, the consortium will find new opportunities for further clinical evaluation of new treatment modalities.

The Research

The clinical trials and registries will not only be aimed at prompt and accurate treatment in the hospital, but also before admission (in the ambulance) and after admission of stroke patients. Their design allows that results can be readily implemented in clinical practice. Studies will demonstrate:

a) how to improve prehospital triage by evaluating prediction rules and devices for diagnosis of the type of stroke and the presences of intracranial vessel occlusion,

b) how to improve the outcome of ischemic stroke by treatment of medium vessel occlusions, by treatment of occlusive and stenotic carotid bifurcation disease, by neuroprotective drugs and by achieving better technical procedural outcome with a personalized technical approach based on thrombus and vessel characteristics,

c) how to improve the outcome of hemorrhagic stroke with minimally invasive interventions, and

d) how to improve post-stroke rehabilitation by better prediction of long-term outcome and the prediction of effects of intervention.

Large clinical datasets will be used to develop models for care organization and individualized treatment strategies, considering individual prognosis based on personal characteristics (sex, age, stroke type, severity), and imaging findings (thrombus and vessel characteristics). The proposed research program will make use of the national stroke research infrastructure established within CONTRAST 1.0 and aims to attract additional public and private funding for fully execution of the research plans.

The overarching aim of CONTRAST 2.0 remains to improve outcome of stroke patients by blending mechanistic, basic scientific projects with pragmatic randomized clinical trials and registries. Specifically, CONTRAST 2.0 will aim to advance treatment through earlier diagnosis of stroke, rapid and more effective personalized treatment of acute stroke, and lastly optimized personalized rehabilitation of stroke survivors in the acute and subacute phase. At the end of the project, it is our ambition to have:

evaluated and implemented the best prehospital triage strategy in the Netherlands resulting in earlier treatment of more patient with stroke.
expanded the indications of EVT to patients with MeVO.
implemented evidence-based guidelines for the optimal treatment timing of carotid occlusive disease.
a preclinical platform for identification of new therapeutic targets and testing of promising therapies, and we have performed the first preclinical trials with neuroprotective agents.
developed personalized EVT approach (technique and device choice) based on thrombus and vessel characteristics.
proven that minimally invasive endoscopy-guided surgery for ICH results in better outcome and we can offer this treatment to all patients in the Netherlands.
assessed the treatment outcomes of advanced endovascular devices for a recently ruptured intracranial aneurysms in the Netherlands and to have initiated an RCT to support evidence-based decision making.
improved prediction of medium-term outcome (defined on multiple domains) of stroke patients to guide the individualized treatment decision of patients 1) in the chain of care and 2) for additional interventions resulting in improved functioning and quality of life.

The origin

Following the world-leading MR CLEAN trial, the CONTRAST 1.0 consortium was formed in 2017 to tackle one of the main challenges on the research agenda of the Dutch Heart Foundation: improving the acute treatment of stroke. Minimizing the burden of disease for everyone who has to live with the consequences of a stroke is also of great importance to the Brain Foundation Netherlands. The Dutch Heart Foundation and the Brain Foundation Netherlands have therefore joined forces to continue the unique and succesful collaboration between acute care and chronic care in 2023. This resulted in the CONTRAST 2.0 consortium. The Dutch Heart Foundation, Brain Foundation Netherlands and ZonMw are partners and funders in the CONTRAST consortium. In addition, this work was funded in part through unrestricted funding by Stryker, Medtronic and Penumbra.

Collaborators

Funded

Contact person:

PhD R. van Nuland (Rick)

rick.vannuland@lygature.org

Principal investigators

Prof. Dr. D.W.J. Dippel (Diederik)

d.dippel@erasmusmc.nl

Dr. C.B.L.M. Majoie (Charles)

c.b.majoie@amsterdamumc.nl

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A healthy lifestyle - a healthy diet and adequate exercise - contribute significantly to chronic disease prevention. People with a lower socioeconomic position (SEP) often have an unhealthier lifestyle than people with a higher SEP. However, interventions aimed at promoting a healthy lifestyle reach precisely this lower SEP target group poorly and may increase social inequality. A possible explanation is that interventions traditionally tend to focus on individual determinants of behavior such as knowledge, attitudes and intentions.
Moreover, these interventions are often not effective, partly because they do not take into account the - social, physical and political - context in which lifestyle choices are made: unhealthy behavior can be seen as an automatic reaction to the 'obesogenic' environment. Changes in and of the environment in which people live can go a long way in promoting healthy lifestyles and reaching all target groups. Changes in the environment should ensure that the healthy choice becomes the easy choice, the obvious choice or even the only choice, especially also for the hard to reach and change target groups such as people with lower education. However, whether environmental interventions are also effective in improving cardiovascular disease risk factors in the longer term is not known and needs to be investigated.
The Research
Supermarkets form one of the most important point-of-choice settings with the potential to directly influence purchasing behaviors. ‘Nudges’ (small environmental encouragements) target the quick, automatic choices and do not require conscious decision making, and pricing strategies can seduce consumers to buy healthier alternatives. Such environmental cues can make it easier to initiate and maintain a healthy lifestyle, and as such, to improve cardiometabolic health. In addition, the use of theory-based mobile applications is an effective way to provide tailored and context-specific feedback on physical activity behaviors through the stimulation of ‘goal setting’ and ‘self-management’. Being incorporated in structures and systems, environmental interventions can make the healthy choice an easy choice for everyone. As such, these types of interventions are especially effective in reaching otherwise difficult-to-reach groups such as people with a lower socioeconomic position (SEP). In particular, a combination of ‘nudging’ (targeting automatic behaviors), ‘pricing’ (responding to the price-sensitivity of low income consumers) and tailored physical activity feedback and support (which works better than general education), seems promising for lowering cardiometabolic risk in individuals with low SEP. Yet, the existing evidence is mostly restricted to short-term effects on (proxies of) health behaviors, and little is known about long-term impact of such integrated interventions on cardiometabolic risk factors.
With SUPREME NUDGE we expand a previous successful Dutch supermarket pricing strategy intervention, and incorporate promising elements such as nudging and ICT applications to provide real-time and context-specific physical activity feedback. We will investigate the effects of this approach on dietary behaviors, physical activity and established cardiometabolic risk factors in adults with a lower SEP. Using principles from Participatory Action Research and systems thinking, we will consult with the relevant stakeholders to explore options for upscaling and further implementation in society. Outcomes will provide policy- and practice relevant evidence with clear, stepwise and realistic leverage points for helping individuals to maintain healthy behaviors and improve their cardiometabolic health by making the healthy choice the easy choice.
SUPREME NUDGE is coordinated by the Amsterdam UMC, location VU University, and includes partners from the VU University, University of Amsterdam, Utrecht University Medical Center, Utrecht University, the Dutch Nutrition Center, Te Velde Research, Nynke van der Laan (ICT developer), Duwtje (creative designers) and supermarket chain Coop.
The origin
The Heart Foundation aims for more people to make healthy choices, so that they feel vital and run less risk of developing (again) cardiovascular diseases, which was one of the themes of the reserach agenda. With its prevention programs, ZonMw contributes to the improvement of prevention practice, to health gains and to reducing socioeconomic health disparities.
Results from research show that healthy behavior cannot be taken for granted, and is strongly influenced by people's social and physical environment and socioeconomic status. Proven effective, innovative and accessible methods to enable people to maintain a healthy lifestyle for a long time are lacking. Therefore, the Dutch Heart Foundation and ZonMw have collaborated to form the program "Gezond leven: goed voor het Hart!". SUPREME NUDGE is one of the projects funded from this program.

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PREDICT 2

2019

Sudden cardiac arrest (SCA) remains a significant public health challenge, accounting for nearly 20% of all deaths in developed nations and approximately half of all heart disease-related fatalities. A notable subset of SCA cases occurs in individuals without prior heart disease diagnosis, resulting in profound psychosocial impacts on affected families and society. Ventricular fibrillation (VF) is the primary arrhythmia leading to SCA, often occurring outside healthcare settings with survival rates ranging from 5% to 20%. Prevention is crucial, yet gaps in our understanding of SCA causes and mechanisms hinder effective prevention efforts. Various genetic and non-genetic factors, such as gender, age, comorbidities, and lifestyle, likely influence SCA risk, but their specific contributions remain unclear.
The Focus
The PREDICT2 initiative brings together leading Principal Investigators with expertise in epidemiology, clinical studies, genetics, and functional research to elucidate factors contributing to SCA, uncover underlying mechanisms, and develop strategies for prevention and treatment.
The Research
Building on foundational work from PREDICT1, which involved extensive patient characterization and preclinical model development, PREDICT2 focuses on inherited arrhythmia syndromes as models to understand the arrhythmogenic substrate in more common cardiac syndromes associated with SCA. Specifically, PREDICT2 aims to:

Identify genetic and non-genetic factors that contribute to SCA risk and develop personalized risk prediction algorithms for individual patient assessment.
Conduct functional studies to elucidate the mechanisms underlying SCA, enabling the development of novel risk stratification and therapeutic approaches.
Implement clinical studies to evaluate risk prediction algorithms and therapeutic interventions, aiming to enhance the treatment and prevention of SCA.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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