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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Atherosclerotic cardiovascular disease (ASCVD) is the main cause of mortality in Europe. During the last decades, successful strategies have been developed to treat ASCVD targeting traditional and novel risk factors leading to an unprecedented arsenal to reduce the cardiovascular disease burden. Unfortunately, current strategies are all aimed at adding novel therapeutic agents on top of the standard therapeutic moieties, adopting the one-size-fits-all dogma. This strategy has major limitations including unaddressed heterogeneity of patients, ignoring patients’ side-effects, lack of response to therapy and decreased compliance. With ATHERONETH, we aim to bring forward stratification tools that help to improve the prediction of the actual cardiovascular risk of individual patients, and in particular the pathophysiological mechanisms the contribute to this risk in the individual patient. This will allow clinicians to better tailor their therapeutic regimens.
The Research

Our main objective is to identify biological parameters that can be utilized to better stratify patients with atherosclerotic cardiovascular disease for improved and personalized prevention and treatment. Utilization can be reached by finding circulating biomarkers or imaging characteristics that reflect plaque phenotypes, underlying pathophysiology, and ASCVD incidence.
By combining frontline knowledge, clinical data resources and multimodal technologies, the consortium members will execute the following workplan.
1 - In ATHERONETH we will fine-tune the local phenotypic diversity of human plaques on a multi-omics level and define plaque types that associate with biology and clinical events. These plaque types will be associated with systemic read-outs (biomarkers).
2 - We will define systemic inflammatory and lipid metabolism related determinants of heterogeneity in plaque phenotype and ASCVD.
3 - We will utilise existing data from (large) cohorts to determine (epi)genetic, lipidomic/proteomic, and microbiome-related biomarkers of ASCVD and build algorithms that define subgroups of patients.
4 -We will study imaging parameters of plaque characteristics and inflammation that point to differential disease progression and potential treatment benefit.
The Origin
AtheroNeth leverages scientific power that was generated over the past decade by (inter)national research consortia. This consortium resulted from the DCVA exploration on atherosclerosis. Our vision for the future is to achieve a reduction in ASCVD-associated morbidity and mortality, an improvement in the quality of life for patients, and a reduction of the associated healthcare burden and costs.
Our program has a strong match with the challenges as reported in the “Nationale Hart en Vaat agenda” (National Cardiovascular Agenda) of the Dutch Heart Foundation. It is evident that the current proposal addresses the challenges “Oog voor verschillen” (Eye for differences) and “Behandel op maat” (Tailored treatment).

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FORSEE

2020

Clinical staff in hospital wards traditionally collect vital signs periodically to assess a patient's cardiorespiratory status, often with intervals of 6 to 10 hours. This method, known as spot-checking, has limitations due to its infrequent nature and dependence on contact sensors, which can be uncomfortable for patients, particularly during sleep.
The Focus
Recent advancements demonstrate that vital signs like heart rate, respiration rate, blood oxygen saturation, and temperature can be monitored remotely using camera-based methods, which are less invasive compared to contact sensors. This innovation could significantly enhance patient comfort by enabling continuous monitoring without the need for frequent interventions by clinical staff. Continuous monitoring also allows for trend analysis of vital signs, offering a comprehensive assessment of a patient's cardiorespiratory condition. Additionally, camera-based methods enable video context analysis, such as detecting patient movements or identifying pain through facial expression analysis. This project explores the use of continuous video monitoring as an unobtrusive method to predict and monitor patient deterioration or adverse events.
The Research
Initially, the feasibility and reliability of camera-based continuous monitoring will be evaluated using data from consenting patients in the ICU at Catharina Hospital in Eindhoven and healthy volunteers. Subsequently, robust technologies will be developed to automatically detect signs of patient deterioration by generating automated early warning scores based on measured vital signs. Throughout the project, feedback from clinical staff and patient experiences will inform the design and implementation of camera-based technologies and early warning systems.
Origin
This project is funded within the Innovative Medical Devices Initiative (IMDI) program 'Heart for Sustainable Care'. The focus of this program is the development of medical technology for the earlier detection, monitoring, and better treatment of cardiovascular diseases to ensure accessible healthcare and sufficient staffing. The program has been developed en funded by the Dutch Heart Foundation, ZonMw and NWO, who collaborate within the Dutch CardioVascular Alliance.

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