We are pleased to invite you to the upcoming event “Stroke: from the acute phase to life after”, which will take place on Tuesday, March 31, from 5:00 pm to 8:00 pm, at MAME – 49 boulevard Preuilly, Tours.
Organized by the Tours-based teams involved in stroke research, this new event will focus on the complexity of the recovery journey after a stroke. The evening will open with a public lecture dedicated to stroke (including intracerebral hemorrhage), its prevention, and its management.
This will be followed by a roundtable discussion bringing together patients, a sociologist, and physicians to explore the challenges of resuming personal and professional life, before a time for discussion with the audience.
Throughout the evening, an exhibition of photographs, paintings, and sculptures created by patients will offer a sensitive insight into the role of artistic activities in the recovery process.
This event follows the public awareness evening held on November 7, 2024, which brought together more than 100 participants. We would be honored to have you join us for this event and contribute to the discussions.
We kindly ask you to confirm your attendance HERE or through the QR code on the invitation.
Please feel free to share this invitation within your network.
This event is organized with the support of the RHU TIPITCH.
Prof. Marco Pasi, Head of the Neurology Department, Stroke Unit Lead, CHRU of Tours Prof. Grégoire Boulouis, Professor of Diagnostic and Interventional Neuroradiology, CHRU of Tours
Intracerebral haemorrhage remains one of the most severe forms of stroke, with a major impact on mortality and long‑term disability. While the first hours are crucial to limiting haematoma expansion, much of the patient’s prognosis is determined in the days that follow.
It is within this often‑overlooked window that DARLENE takes place, developed as part of Work Package 3 of the RHU TIPITCH, and dedicated to a central challenge: modulating post‑haemorrhagic inflammation.
Perihaemorrhagic Oedema: A Key Determinant of Outcome
When an intracerebral haemorrhage occurs, the bleeding itself represents only the first stage of the cerebral injury. The sudden entry of blood into brain tissue destroys cells at the point of impact and triggers an intense inflammatory reaction.
This inflammatory response leads to the formation of perihaemorrhagic oedema, which progressively develops over the following days. This oedema exerts mass effect on the surrounding brain and worsens the initial injury. Its severity is closely linked to functional outcome:
the larger the oedema, the higher the risk of severe disability or death.
Physiologically, this inflammation results from the activation of resident brain immune cells — microglia — as well as the recruitment of inflammatory cells from the bloodstream. It is accompanied by breakdown of the blood–brain barrier, promoting accumulation of fluid and inflammatory cells in brain tissue.
An Ambivalent Process That Cannot Simply Be “Blocked”
While excessive inflammation is clearly harmful, it is not solely detrimental. It also plays an essential role in haematoma clearance and tissue repair.
This is the core complexity of the problem:
- blocking inflammation indiscriminately may hinder essential repair mechanisms;
- allowing it to unfold without intervention may lead to dangerous inflammatory escalation.
DARLENE is built on this nuanced understanding: the aim is not to suppress inflammation, but to modulate it — tempering its harmful components while preserving its beneficial effects.
An Unmet Therapeutic Need
In clinical practice, there is currently no validated medication specifically targeting inflammation after intracerebral haemorrhage. Corticosteroids have not shown benefit, and previous anti‑inflammatory trials have not demonstrated convincing clinical efficacy.
This lack of therapeutic options stands in stark contrast with the major role played by cerebral oedema in patient outcomes. DARLENE was born from this observation: a key determinant of prognosis remains therapeutically unaddressed.
DARLENE Within the TIPITCH Trajectory: An Integrated Approach
The DARLENE study fits perfectly within the global logic of TIPITCH, which targets the different stages of intracerebral haemorrhage:
- upstream, limiting vascular rupture and haematoma expansion;
- intermediate, reducing blood toxicity and promoting its evacuation;
- later, targeting inflammation and optimising repair mechanisms.
DARLENE corresponds to this third pillar. It complements early‑stage strategies by addressing a slower process that is equally decisive for long‑term functional outcome.
A Strong Biological Rationale: The NRF2 Pathway
The therapeutic choice evaluated in DARLENE is based on years of translational research, from experimental models to human observations. These studies highlight the central role of the NRF2 pathway in regulating post‑haemorrhagic inflammation.
NRF2 contributes both to:
- limiting excessive inflammatory mechanisms,
- supporting haematoma resolution and brain tissue repair.
The study evaluates the effect of an NRF2 agonist, Diroximel fumarate, using a drug‑repositioning strategy. Already authorised for other indications, it benefits from extensive safety data — a major asset for future potential clinical use.
A Clinical Study Designed Around Biological Time
DARLENE is a Phase 2B randomised, multicentre clinical trial, sponsored by CHU Lille and involving several French centres specialised in stroke care. Nearly 200 patients with spontaneous intracerebral haemorrhage will be enrolled.
One of the study’s most innovative aspects is the 21‑day treatment duration. This timeframe was defined to accompany the full course of inflammation, from oedema development to tissue repair.
The primary endpoint is the radiological measurement of cerebral oedema volume, supplemented by clinical criteria and close monitoring of treatment tolerance.
A Scientific and Human Innovation
Beyond its therapeutic approach, DARLENE stands out for its thoughtful organisation and follow‑up. The protocol benefited from the input of patients who had themselves experienced intracerebral haemorrhage, enabling adjustments to monitoring procedures and evaluation tools to reflect real‑world patient experience.
Furthermore, biological samples collected during the study will constitute a biobank, paving the way for future research on inflammation mechanisms and biomarkers of treatment response.
Long Term Prospects, Without Premature Promises
If DARLENE yields positive results, it will represent a major proof of concept, paving the way for a larger Phase 3 trial. The long‑term objective is clear:
to develop an accessible treatment that complements existing strategies and sustainably improves patient outcomes.
More broadly, DARLENE embodies the philosophy of TIPITCH:
challenging the perceived inevitability of intracerebral haemorrhage through rigorous, innovative, patient‑centred science.
Understanding and predicting inflammation after brain haemorrhage: the INFINITE study takes centre stage
A neurologist at Toulouse University Hospital and a specialist in intracerebral haemorrhage and advanced imaging (MRI, PET), Pr Nicolas Raposo coordinates the scientific and technical aspects of the INFINITE study (Role of neuroINFlammation, and blood‑brain barrier breakdown IN InTracerebral haemorrhagE) within TIPITCH. After spending time at Harvard University in Boston — where he met two other TIPITCH contributors, Pr Grégoire Boulouis and Pr Marco Pasi (CHRU Tours) — he now leads several major studies on intracerebral haemorrhage.
He explains here the scientific ambitions of INFINITE, a project unprecedented in France and internationally.
“INFINITE explores a missing link: understanding neuroinflammation before it becomes visible on CT scan.”
What is the main objective of the INFINITE study, and how does it fit within TIPITCH?
INFINITE is part of Work Package 3, which focuses on reducing inflammation caused by brain haemorrhage.
Within this module, we also find the DARLENE study, which tests a pharmacological treatment aimed at modulating the inflammatory response. It is, in some sense, the final step of the module: testing the drug.
INFINITE is positioned further upstream in the process:
its goal is to better understand, detect and quantify neuroinflammation around the haematoma, using modern imaging tools that may be more sensitive than standard imaging.
CT scan currently shows the oedema surrounding the haematoma, which likely represents a late stage of the neuroinflammatory cascade after intracerebral haemorrhage. But thanks to animal models, we know that inflammation begins within the very first hours. INFINITE aims to assess whether modern tools can capture neuroinflammation earlier than CT.
“We want to image an inflammation that remains invisible on conventional imaging.”
Which tools are you using to detect this very early inflammation?
The study relies on three complementary modalities:
- A TSPO PET scan, which visualises microglial activation — a marker of neuroinflammation.
- Advanced MRI, using a specific sequence (DCE‑MRI) to image blood–brain barrier disruption, a key feature of oedema.
- Blood sampling to measure inflammatory biomarkers.
All examinations take place 10 days after the haemorrhage (Day 10), and patients are seen again at 6 months to assess neurological recovery using the modified Rankin Scale.
Our hypothesis is that patients with poorer neurological recovery at 6 months are those who showed more marked early neuroinflammation.
This study will determine whether early measurement of inflammation can predict clinical outcomes.
“INFINITE could help better identify future candidates for anti‑inflammatory treatments.”
What is the connection with the DARLENE trial?
DARLENE will test a drug targeting inflammation. But, as is often the case, not all patients may respond in the same way.
INFINITE aims to provide tools to:
- identify patients with significant neuroinflammation, and
- potentially predict who stands to benefit most from treatments such as that evaluated in DARLENE.
In other words, INFINITE could become a stratification tool for future therapeutic trials.
“INFINITE is a rare multicentre study — almost unique worldwide.”
Which centres are participating, and why these centres?
Three centres are involved:
- CHU Toulouse
- CHU Bordeaux (Pr Igor Sibon, PI)
- CHU Montpellier (Dr Adrien Ter Schiphorst, PI)
Why not more?
Because the imaging used — a specific PET radiotracer, DPA‑714 — has a very short half‑life.
It is produced in Toulouse, which requires geographical proximity.
Moreover, very few centres are able to perform, in patients in the acute phase of intracerebral haemorrhage:
- a PET scan,
- an advanced MRI,
- and blood sampling,
all on the same day.
INFINITE is therefore both a demanding and highly specialised study.
An ambitious study supported by exceptional expertise and resources
What is the planned sample size and timeline?
The study will include 117 patients over approximately 36 months, with a launch planned for spring 2026.
This is an ambitious target, as performing such imaging in this clinical context is rare and complex. To date, worldwide, only two studies have combined PET scan and MRI of the blood–brain barrier in the acute phase of intracerebral haemorrhage — and each on fewer than 10 patients.
INFINITE will therefore be one of the first multicentre studies of this scale.
“The ultimate goal: understand, predict, and treat better.”
What are the next steps if your hypotheses are confirmed?
If INFINITE shows that neuroinflammation measured at Day 10 is a key factor in poor prognosis, several advances could follow:
- better selection of candidates for therapeutic trials such as DARLENE,
- the development of more personalised treatments,
- improved timing of intervention,
- and ultimately, better neurological outcomes for patients with intracerebral haemorrhage.
INFINITE is therefore a strategic piece of the TIPITCH puzzle: better understanding to treat better.
Any final thoughts?
Pr Raposo wishes to thank all TIPITCH partners for their support and enthusiasm, as well as the scientific and methodological teams in Toulouse (Inserm U1214 TONIC, Clinical Investigation Centre), and the investigator sites in Bordeaux and Montpellier, whose expertise in advanced imaging has made it possible to structure such an ambitious study.
Key expertise mobilised for INFINITE
The INFINITE study is built on a particularly strong foundation of expertise in Toulouse.
- Pr Pailloux, nuclear medicine specialist, brings unique experience with the DPA‑714 PET radiotracer, essential for visualising neuroinflammation.
- Patrice Peran leads advanced analysis of MRI sequences, particularly those assessing blood–brain barrier disruption.
- Dr Claire Thalamas and the team from the Clinical Investigation Centre at CHU Toulouse ensured methodological structuring of the study — from design to sample size calculation — a decisive contribution to carrying out such an ambitious protocol.
🔬 We are delighted to announce the participation of Dr Maxime Baudouin, Prof. Aymeric Rouchaud, and Caroline Croguennec from CHU Limoges, all members of the TIPITCH project, at this key event.
A great opportunity to showcase their expertise and keep up with the latest innovations in interventional neuroradiology!
💡 TIPITCH: a synergy of expertise
TIPITCH brings together diverse and complementary fields—from neurology and neuroradiology to neurosurgery, neuro‑ICU, and advanced imaging—uniting researchers, clinicians, hospital teams, industry partners and patient associations to improve the management of haemorrhagic stroke.
We are proud to count among us committed experts working towards this essential mission.
📅 Follow the congress online: https://lnkd.in/esW3eyR8
📌 Discover the programme: https://lnkd.in/MUP7
🔍 Together, let’s take care of our brains!
As part of RHU TIPITCH – Transforming the Prognosis of Haemorrhagic Stroke, we are committed to improving the management of haemorrhagic strokes by exploring new therapeutic approaches.
At the International Stroke Conference 2025 #ISC2025, experts shared major advances in the treatment of deep intracerebral haemorrhage—an issue at the very heart of our project.
🔹 Minimally invasive surgery: what progress is being made?
– MISTIE and MIPS, two innovative techniques for haematoma evacuation, show promising results but still require further study to demonstrate a clear functional benefit.
– Decompressive surgery, assessed in the SWITCH trial, remains a debated option with no confirmed improvement in six‑month recovery outcomes.
🔹 What levers for better medical management?
Professor Charlotte Cordonnier, lead investigator of TIPITCH, emphasised the importance of combined strategies to limit haematoma expansion, reduce cerebral oedema, and promote clot resolution. New avenues are emerging, particularly around modulation of the inflammatory response.
These advances strongly align with our mission: improving the treatment of haemorrhagic stroke and optimising care pathways.
📌 The key challenge for upcoming studies?
Identifying the patients most likely to benefit from these combined approaches and refining evaluation criteria.
👉 We will continue to share major developments on this topic.
On Tuesday 18 March, Professor Grégoire Boulouis and Professor Charlotte Cordonnier, members of the RHU TIPITCH consortium, had the honour of taking part in a session of the French National Academy of Medicine dedicated to spontaneous cerebral haemorrhages.
A prestigious moment to share scientific advances on this complex and still too often misunderstood condition.
💡 Artificial intelligence serving diagnosis and monitoring of haemorrhagic stroke
As part of his presentation on “Imaging: diagnosis and monitoring”, Professor Grégoire Boulouis (CHRU Tours) highlighted the central role of imaging and answered questions on artificial intelligence, emphasising the work underway within the TIPITCH project:
“Within the TIPITCH project, we are leading working groups in Tours to develop a large-scale imaging infrastructure and database. The aim is to gather a sufficiently large volume of data to train artificial intelligence algorithms. Structuring these data is a crucial step to enable efficient automated analysis. As of today, such a tool does not yet exist, but it is a major objective we hope to achieve.”
💡 Transforming the management of haemorrhagic stroke
Speaking on “Treatments: future therapeutic targets”, Professor Charlotte Cordonnier (CHU Lille), lead investigator of RHU TIPITCH, highlighted the major shift currently taking place in the management of haemorrhagic stroke:
“Thanks to the work undertaken, particularly within TIPITCH, we are moving away from an approach characterised by nihilism and self‑fulfilling pessimism towards a more optimistic vision based on a multidisciplinary strategy. As illustrated during this session, the management of cerebral haemorrhage now relies on close collaboration between neurologists, neuroradiologists, neurosurgeons and neuro‑intensive care specialists. Imaging and invasive treatments are integrated from the moment the patient is admitted, within a multimodal care environment that significantly improves overall management.”
👏 Congratulations to Charlotte Cordonnier, whose presentation generated strong interest, as reflected in the many questions that followed!
🎥 Replay available: https://lnkd.in/gmw73Cmw
📌 Prof. Boulouis at 1:38 · Prof. Cordonnier at 1:55
Our warmest congratulations to both experts for their commitment to research and innovation in neurology!
🔬 The RHU TIPITCH project was represented by Professor Charlotte Cordonnier, project lead from CHU Lille, at the International Stroke Conference 2025 – #ISC25, held in Los Angeles, USA, from 4 to 7 February, during the session dedicated to haemorrhagic stroke.
💡 Transforming the prognosis of patients with intracerebral haemorrhage requires a collaborative and multidisciplinary approach. The discussions at this event reinforced the importance of innovating and rethinking the management of these severe strokes.
👏 Thank you to Professor Cordonnier and to all the experts of the TIPITCH consortium who are committed to this essential mission.
Together, let’s continue moving forward!
One of our partners, Aymeric Rouchaud, is looking for new talent to strengthen his teams and contribute to a major research initiative: #TIPITCH! 🚀
💼 Open position: Project Manager & Assistant Engineer
🔬 Mission: Successful candidates will be responsible for coordinating projects from initial design through to the structuring and delivery of results.
👉 Would you like to put your skills to work in support of medical research and innovation?
Join us and take part in this collective ambition!
