Evaluation of Deferiprone for Long-term Iron Chelation in Preventing Secondary Neurodegeneration Post-Stroke in Patients with Proximal Sylvian Artery Occlusion

The primary objective of this study is to evaluate the effect of prolonged treatment with **deferiprone** (Ferriprox®) on iron accumulation in patients with proximal occlusion of the sylvian artery following a stroke. The treatment involves administering deferiprone daily at a low dose (30 mg/kg/day) from day 3 to day 5 post-stroke, continuing for six months. The study aims to compare the evolution of iron accumulation, measured by the 95th percentile of R2* values, between an initial MRI on day 5 and at six months within the homolateral black substance initially spared by the infarction. This is compared to values measured without treatment in previous research. The clinical relevance of this objective lies in its potential to prevent secondary remote degeneration after a stroke, which could improve patient outcomes.

Secondary objectives include: - Comparing the effect of prolonged deferiprone treatment on the evolution of iron accumulation within the homolateral thalamus, initially spared by the infarction, and clinical performance at six months, compared to untreated patients. - Comparing voxel-to-voxel the evolution of iron load, using the 95th percentile of R2* values and QSM measurements, between an initial MRI and at six months post-sylvian infarction within the black substance, thalamus, and the whole brain, between treated and untreated patients.

The clinical trial involves participants diagnosed with **stroke**, specifically those with proximal occlusion of the sylvian artery. The study population includes both male and female subjects, aged 18 years and older. Participants are required to have a stroke involving the deep territory of the middle cerebral artery, affecting at least half of the striatum's volume. The trial includes individuals who are covered by social insurance and have an absolute neutrophil count of at least 1.5 x10⁹/L. Women of childbearing potential must have a negative β HCG test and use effective contraception, while male participants must ensure their partners use highly effective contraception or agree to use a condom during and after treatment. The trial population is considered vulnerable, and informed consent is obtained from participants or their representatives. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **deferiprone** in preventing secondary degeneration following a **stroke**. This study is a randomized, double-blind, controlled trial with a duration of six months. Participants will be randomly assigned to receive either deferiprone or a placebo, with the primary objective being to assess the variation in iron accumulation as measured by R2* values between baseline and six months. The trial will include several key visits: an initial screening visit, follow-up visits at three and six months, and an end-of-study visit. The screening visit will determine eligibility based on criteria such as age, medical history, and specific stroke characteristics. Follow-up visits will monitor the progression of iron accumulation and assess clinical outcomes using various scales, including the Fugl-Meyer scale and the Montreal Cognitive Assessment. The end-of-study visit will conclude the participant's involvement and gather final data for analysis.

Participants are expected to be involved in the study for a total of six months, with the possibility of early termination if they experience adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial will measure primary endpoints such as the variation of iron in the substantia nigra ipsilateral to the stroke, while secondary endpoints will include iron variation in the thalamus and clinical scores related to functional and cognitive outcomes. The study aims to provide insights into the potential benefits of deferiprone in managing post-stroke complications, with the ultimate goal of improving patient outcomes through targeted iron chelation therapy.

The clinical trial involves the administration of **Ferriprox 500 mg film-coated tablets**, which contain the active substance **deferiprone**. This medication is utilized for its iron-chelating properties and is administered orally. The pharmaceutical form is a film-coated tablet, ensuring ease of ingestion and controlled release of the active ingredient. The dosage regimen for this trial is set at 30 mg/kg per day, with the treatment period extending up to six months. The administration begins between the third and fifth day post-stroke, continuing daily to assess its efficacy in preventing secondary remote degeneration after a stroke. The maximum daily and total dose is maintained at 30 mg/kg to ensure safety and efficacy.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are employed. The focus remains solely on the effects of deferiprone as an iron chelator. Participant compliance is monitored through regular assessments and follow-ups to ensure adherence to the dosing schedule and to evaluate the therapeutic outcomes. The trial aims to measure the evolution of iron accumulation using MRI scans, comparing initial and six-month post-treatment values to determine the effectiveness of deferiprone in mitigating iron-related complications post-stroke.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves the evaluation of iron accumulation using the R2* value (95th percentile) measured by MRI. This assessment will be conducted between a baseline MRI, performed before day 5, and a follow-up MRI at 6 months. The focus will be on the **substantia nigra** ipsilateral to the stroke in patients randomized to receive Deferiprone.

Secondary endpoints include the variation of iron as measured by R2* within the thalamus ipsilateral to the stroke, as well as the use of quantitative susceptibility mapping (QSM) for voxel-by-voxel quantification. These measurements will also be compared between the baseline and 6-month MRIs. Additionally, clinical scores will be evaluated at 3 and 6 months, assessing functional outcomes using the upper limb Fugl-Meyer scale, the Box and Block test, and the modified Rankin scale (mRS). Cognitive outcomes will be measured by the Montreal Cognitive Assessment (MoCA), and mood disorders will be assessed using the Center for Epidemiologic Studies Depression Scale (CESD) and the Generalized Anxiety Disorder Scale (GAD-7).