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

May 27, 2026 updated by: University Hospital, Lille

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

Spontaneous intracerebral haemorrhage (ICH) is a life-threatening condition, still devoided of specific treatment. Peri-haematomal oedema (PHO) develops in the ensuing days after ICH onset and worsens functional outcome. Hence, PHO is a promising therapeutic target but until now there is no specific treatment for PHO. The occurrence and growth of PHO is mainly mediated by inflammation. We hypothesize that a modulation of inflammation is effective in reducing PHO growth, therefore improving the functional outcome of ICH patients. From animal studies to human post-mortem studies, our team has demonstrated a key role for erythroid-related nuclear factor 2 (Nrf2) in PHO. Indeed, this transcription factor promotes the protective effect of inflammation: Nrf2 activation enhances antioxidant defenses and increases rates of blood resorption. Therefore, Nrf2 emerges as a promising and innovative therapeutic target. Taking into account the prolonged time interval between de novo drug discovery and use in clinical practice, drug repurposing is an interesting option for the unmet clinical need of reducing PHO. We chose Diroximel Fumarate (DRF) which is a safe and effective Nrf2 activator widely used in multiple sclerosis (dimethyl fumarate is on the market since 2013, and DRF since 2019) to modulate inflammation and to establish the efficacy of Nrf2 activation in reducing PHO growth and, ultimately, in improving the functional prognosis after ICH.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

192

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DRF group
2*231 mg of Diroximel Fumarate (DRF) per day for 7 days then 4*231 mg per day for 14 days.
Drug: DRF
2*231 mg of Diroximel Fumarate (DRF) per day for 7 days then 4*231 mg per day for 14 days.
Placebo Comparator: Placebo group
2 capsules of matching placebo per day for 7 days than 4 capsules of matching placebo per day for 14 days.
Drug: Placebo
2 capsules of matching placebo per day for 7 days than 4 capsules of matching placebo per day for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Absolute volume of PHO assessed at 8 ± 1 days with brain non-contrast CT (NCCT) scan.
Time Frame: at 8 ± 1 days
at 8 ± 1 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Functional outcome: global disability assessed by overall distribution of mRS score at 6 months (end of follow-up) (shift analysis)
Time Frame: at 6 months
at 6 months
The rate of severe adverse events occurring between the date of randomization and the end of follow-up (six-month visit).
Time Frame: At 6 months
At 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

Ministère de la Santé

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

November 27, 2025

First Submitted That Met QC Criteria

November 27, 2025

First Posted (Actual)

December 10, 2025

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024_0474
  • 2025-522687-33-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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