N-ACETYLCYSTEINE FOR THROMBOLYSIS IN ACUTE STROKE

Study Overview
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Brief Summary
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The primary objective of the study is to assess the safety of N-Acetylcysteine as a thrombolytic agent in acute ischemic stroke, especially regarding the risk of hemorrhagic transformation.

Detailed Description
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Preclinical studies demonstrated that N-Acetylcysteine (NAC) is able to break von Willebrand Factor (VWF) multimers by bisulfide bond reduction. Since thrombi in stroke patients are rich in VWF, NAC could be used as a thrombolytic agent during the acute phase. This study aims at assessing the safety of NAC in combination with alteplase (rt-PA) at the acute phase of ischemic stroke.

Official Title
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TOLERANCE STUDY OF N-ACETYLCYSTEINE FOR THROMBOLYSIS IN THE ACUTE PHASE OF ISCHEMIC STROKE / ETUDE DE TOLERANCE DE LA N-ACETYLCYSTEINE POUR LA THROMBOLYSE A LA PHASE AIGUË DE L'INFARCTUS CEREBRAL

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: N-Acetyl cysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient presenting with an acute ischemic stroke (non lacunar) as assessed by cerebral imaging (either CT or MRI), with or without visible vessel occlusion. Patient eligible to intravenous thrombolysis according to current criteria, including patients who will also benefit from endovascular treatment (if eligible). Personal or familial consent to participate in the study. Exclusion Criteria: Known hypersensitivity to N-Acetylcysteine or to any excipient from the formulation. Coma and/or NIHSS <4 or ≥20. Daily treatment with Nitrovasodilator before the inclusion. Known asthma or chronic obstructive pulmonary disease requiring bronchodilatators or steroids. Participation to another interventional study if it requires administration of an experimental treatment in the first 3 days after NAC treatment. Women of childbearing age (age < or = to 50) Known history of prior treatment with vitamin-K antagonist or direct oral anticoagulant. Known history of severe hepatopathy including cirrhosis, portal hypertension (esophageal varices) and evolutive hepatopathy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 86 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetylcysteine 150 mg/kg<br>Single intravenous injection of N-Acetylcysteine (150 mg/kg in 15 minutes). | Drug: N-Acetyl cysteine<br>* Administered as specified in the treatment arm<br>* Other names: HIDONAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic intracranial hemorrhagic transformation | Rate of symptomatic hemorrhagic transformation according to the SITS-MOST criteria: a local or remote parenchymal hemorrhage on imaging 22 to 36 hours after treatment or earlier if the imaging scan was performed due to clinical deterioration combined with a neurological deterioration of >4 NIHSS points from baseline or from the lowest NIHSS score between baseline and 24 hours or leading to death within 24 hours. | 22 to 36 hours after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracranial hemorrhagic events | Rate of extracranial hemorrhagic events | Up to 3 months after treatment | 
| Treatment related side effects | Rate of any drug related side effects according to the Common Terminology Criteria of Adverse Event 5.0. | Up to 3 months after treatment | 
| Mortality and functional independence | Rate of mortality and functional independence at 3 months according to the modified Rankin scale (mRs) | 3 months after treatment | 
| Early neurological improvement | Rate of early neurological improvement defined as an improvement of >4 NIHSS points 24 hours after treatment. | 24 hours after treatment | 
| Plasma VWF multimers | Mean size of VWF multimers before and after treatment | Before, at 3 hours and at 24 hours after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombolysis, Hemorrhagic transformation, Alteplase, Thrombectomy