N-ACETYLCYSTEINE FOR THROMBOLYSIS IN ACUTE STROKE

Phase 2

• Conditions: Stroke, Ischemic
• Interventions: Drug: N-Acetyl cysteine

• Registration Number: NCT04920448
• Lead Sponsor: University Hospital, Caen

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.

Study Timeline

• Status Verified: 2021-06
• Study First Submitted: 2021-06-03
• Study First Submitted QC: 2021-06-03
• Last Update Submitted: 2021-06-03
• Study Start: 2021-06-07
• Study First Posted: 2021-06-09
• Last Update Posted: 2021-06-09
• Primary Completion: 2022-06-08
• Study Completion: 2022-09-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
N-Acetylcysteine 150 mg/kg	N-Acetyl cysteine	Single intravenous injection of N-Acetylcysteine (150 mg/kg in 15 minutes).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
Extracranial hemorrhagic events	Up to 3 months after treatment	Rate of extracranial hemorrhagic events
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

Trial Locations

Locations (1)

CHU Caen; 🇫🇷 Caen, Normandy, France