Clinical trial NCT04920448: N-ACETYLCYSTEINE FOR THROMBOLYSIS IN ACUTE STROKE
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stroke, Ischemic
Keywords: Thrombolysis
Hemorrhagic transformation
Alteplase
Thrombectomy
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2021-06-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 86
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Symptomatic intracranial hemorrhagic transformation
timeFrame: 22 to 36 hours after treatment
Secondary outcomes:
measure: Extracranial hemorrhagic events
timeFrame: Up to 3 months after treatment
measure: Treatment related side effects
timeFrame: Up to 3 months after treatment
measure: Mortality and functional independence
timeFrame: 3 months after treatment
measure: Early neurological improvement
timeFrame: 24 hours after treatment
measure: Plasma VWF multimers
timeFrame: Before, at 3 hours and at 24 hours after treatment
Other outcomes:
Locations:
city: Caen
country: France
facility: CHU Caen
state: Normandy
Study officials:
References:
citation: Martinez de Lizarrondo S, Gakuba C, Herbig BA, Repesse Y, Ali C, Denis CV, Lenting PJ, Touze E, Diamond SL, Vivien D, Gauberti M. Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi. Circulation. 2017 Aug 15;136(7):646-660. doi: 10.1161/CIRCULATIONAHA.117.027290. Epub 2017 May 9.