Stroke, Ischemic
Conditions
Keywords
Thrombolysis, Hemorrhagic transformation, Alteplase, Thrombectomy
Brief summary
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
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.
Interventions
DRUGN-Acetyl cysteine
Administered as specified in the treatment arm
Sponsors
University Hospital, Caen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 86 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptomatic intracranial hemorrhagic transformation | 22 to 36 hours after treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extracranial hemorrhagic events | Up to 3 months after treatment | Rate of extracranial hemorrhagic events |
| Treatment related side effects | Up to 3 months after treatment | Rate of any drug related side effects according to the Common Terminology Criteria of Adverse Event 5.0. |
| Mortality and functional independence | 3 months after treatment | Rate of mortality and functional independence at 3 months according to the modified Rankin scale (mRs) |
| Early neurological improvement | 24 hours after treatment | Rate of early neurological improvement defined as an improvement of \>4 NIHSS points 24 hours after treatment. |
| Plasma VWF multimers | Before, at 3 hours and at 24 hours after treatment | Mean size of VWF multimers before and after treatment |
Countries
France
Outcome results
None listed