Diroximel fumarate to reduce swelling around a brain bleed

DIROXIMEL FUMARATE TO REDUCE PERIHAEMATOMAL OEDEMA IN INTRACEREBRAL HAEMORRHAGE: A DOUBLE BLIND RANDOMIZED CLINICAL TRIAL (DARLENE)

This trial tests whether diroximel fumarate can reduce swelling around the bleed in adults with spontaneous intracerebral hemorrhage when started within 48 hours.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Lille (other)
• Locations: 1 site (Lille)
• Trial ID: NCT07275515 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled phase 2 multicenter trial of diroximel fumarate (DRF) versus placebo in adults with supratentorial spontaneous intracerebral hemorrhage. Study treatment is given no later than 48 hours after symptom onset and patients are followed with brain imaging to measure peri‑hematomal edema growth and with clinical scales for functional outcome. Key exclusions include very large hematomas, severe coma, pure intraventricular hemorrhage, secondary causes such as trauma or vascular malformation, and planned surgical evacuation. The intervention aims to modulate inflammation via Nrf2 activation to limit edema and promote blood resorption.

Who should consider this trial

Good fit: Adults (≥18 years) with a confirmed supratentorial spontaneous intracerebral hemorrhage who can start the study drug within 48 hours, can provide consent, and have French social insurance are ideal candidates.

Not a fit: Patients with massive hematomas (>60 ml), severe coma (GCS <6), pure intraventricular hemorrhage, ICH from trauma or other secondary causes, or those requiring immediate surgical evacuation are unlikely to benefit.

Why it matters

Potential benefit: If successful, the drug could limit peri‑hematomal swelling and improve recovery and long‑term function after intracerebral hemorrhage.

How similar studies have performed: Preclinical animal studies and human post‑mortem data support Nrf2 activation as protective, but clinical testing of Nrf2‑targeting agents in ICH is novel and has not yet demonstrated established clinical success.

Eligibility criteria

Inclusion Criteria:

1. Patients 18 years or older (no upper age limit)
2. Patients admitted for a first-ever or recurrent (occurred more than 1 year before) symptomatic supratentorial spontaneous ICH confirmed by brain imaging
3. Administration of study treatment no later than 48 hours after symptom onset or since last seen normal
4. Written consent obtained
5. Patient with social insurance in France
6. Patient willing to comply with all study procedures and duration

Exclusion Criteria:

1. Massive ICH for Investigational medicinal product seems futile (hematoma volume is estimated \> 60ml)
2. Severe coma (Glasgow Coma Scale \<6)
3. Pure intraventricular hemorrhage
4. ICH suspected to result from a preceding trauma, an identified intracranial vascular malformation, venous thrombosis, tumor or hemorrhagic transformation within an infarct
5. Patient planned for surgical evacuation of ICH before randomization (Evacuation, Decompressive hemicraniectomy, External ventricular drain)
6. Patient with a known indication for DRF treatment (e.g. multiple sclerosis) or any other NrF2 agonist (dimethyl fumarate; Tecfidera)
7. Patient with contraindication to DRF: patients with known hypersensitivity to DRF, or to any of the excipients of VUMERITY (patients taking dimethyl fumarate)
8. Severe lymphopenia at admission (lymphocyte counts \< 0.5 x 109/L)
9. Medical history: Suspected or confirmed of progressive multifocal leukoencephalopathy
10. Severe swallowing disorder and/or nasogastric tube required
11. Severe pre-ICH dependency (modified Rankin score of 5)
12. Life expectancy \< 1 year related to comorbidities
13. Late-stage organ (acute cardiac, renal or hepatic failure)
14. Decision already taken for palliative (end of life) care with withdrawal of active treatment
15. Pregnancy or breastfeeding or Women of childbearing age without effective contraception (a pregnancy test will be done)
16. Adults who are deprived of their liberty by judicial or administrative decision

Where this trial is running

Lille

• CHU de Lille — Lille, France (RECRUITING)

Study contacts

• Study coordinator: Laurent PUY

Conditions: Stroke, proof of concept, multicenter, stroke, randomization, double-blind, placebo-controlled, France, DRF group VS Placebo group