The MaTRISS 2 study is a phase 2 randomized, double-blinded and placebo-controlled trial aimed at recruiting 60 subjects (30 placebo and 30 active) from 15 stroke centers in France. The main objective will be to assess the efficacy of OTR4132-MD in patients with anterior ischemic stroke after endovascular thrombectomy. One dose will be tested (2 mg) against placebo. The main outcomes will be NIHSS (neurological score) at 24 hours, rate of intracranial hemorrhages at 24 hours, MRI lesion volume at 3 months and neurological scores at 3 months.

• The aim of the study is to confirm previous safety and encouraging efficacy data obtained from the MATRISS first-in man study and animal studies.

  . This is a prospective double-blinded placebo-controlled trial. The trial will recruit 60 subjects (30 per group) with anterior circulation acute ischemic stroke (AIS) re-vascularized (TICI score 2b - 3) by endovascular thrombectomy. Subjects will be followed for 3 months after a single administration of OTR4132-MD or placebo.

• The study is double blinded and there is no way to distinguish the active product from the placebo. Neither the treating nor evaluating physicians, nor the patients, will be informed of the allocation of the treatment before database lock and the end of the trial.

• The use of a placebo is justified by the absence of any neuroprotector approved in France in this indication so there is no comparator. The administration of OTR4132-MD or Placebo will be done in addition to the best standard of care and does not result in any additional po-tentially harmful procedure.

• The study will include 60 patients (30 in the active group and 30 in the placebo group) which is considered sufficient to demonstrate superiority of treatment over placebo with a 5% risk two-sided level (see sample size calculation).

• The study will evaluate a single dose of OTR4132-MD (2 mg) over Placebo. This dose has been selected as the highest and safest dose tested in the previous MATRISS dose-escalation study.

• A 3 months-follow-up period is estimated sufficient to evaluate the residual disability and is recommended in the guideline "Points to consider on clinical investigation of medicinal products for the treatment of acute stroke" (EMA, 2001, CPMP/EWP/560/98).

• A Data Safety Monitoring Board (DSMB) will be set up. It will consist of three medical experts in neurology and stroke trials. Other relevant expertise will be consulted if deemed neces-sary. The members of the committee will review interim blinded safety and efficacy study da-ta. Unblinding procedures will be set up in individual cases if deemed necessary.

Inclusion Criteria:

1. Age between 18 and 85 years

2. Acute ischemic stroke in anterior circulation territory, identified by magnetic resonance imaging (MRI).

3. Occlusion of anterior circulation i.e. carotid artery (ICA) or proximal middle cerebral artery (MCA) (M1 and/or M2 segment)

4. Endovascular thrombectomy (with or without previous intravenous thrombolysis)

5. Recanalization confirmed by angiography after endovascular treatment: TICI grade 2b - 3

6. NIHSS (National Institute of Health Stroke Scale/Score) ≥ 11

7. Pre-stroke modified Rankin Score (mRS): 0 or 1

8. Patient* or legally authorized representative (family member or trusted person if patient unable to give consent) or independent physician (if patient unable to give consent and if an authorized representative cannot be reached) has signed informed consent.

   • Patients unable to give consent at baseline will go through a deferred consent procedure to continue the study

Exclusion Criteria:

1. Previous symptomatic stroke with permanent sequelae
2. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological evaluation
3. Contraindication to MRI
4. Stroke lesion not visible on MRI
5. History of allergy or anaphylactic reactions to any of the ingredients of OTR4132-MD or heparinoids
6. History of hypersensitivity or anaphylactic reactions to iodinated contrast media
7. Intracranial tumor at inclusion
8. Pregnant or breastfeeding women
9. Severe renal failure with glomerular filtration rate (GFR) < 30 mL/min
10. Severe uncontrolled arterial hypertension e.g. systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg, or intravenous medication necessary to reduce blood pressure
11. Life expectancy of less than 3 months or co-morbidities that could influence the study results or would complicate assessment of outcomes (e.g. dementia, psychiatric disease) or would make clinical follow-up difficult
12. Increased risk of hemorrhage (for instance medical history of significant bleeding disorders, major surgery or significant trauma in the past 3 months, any history of suspected intracranial hemorrhage, symptoms suggestive of subarachnoid hemorrhage, even if the MRI is normal, international normalized ratio (INR)>1.3 or activated partial thromboplastin time (aPTT)>ULN (upper limit of normal)
13. Suspected cerebral vasculitis based on medical history and imaging
14. Occlusions in multiple vascular territories
15. Evidence of any prior intracranial intervention (i.e. neurosurgery, endovascular intervention)
16. Worsening of medical or neurological conditions or per-procedures complications
17. Any other serious, advanced, or terminal illness (investigator judgment)
18. Current participation in another therapeutic investigation (drug or device)
19. The patient is not a member or beneficiary of the French social security system