N-ACETYLCYSTEINE FOR THROMBOLYSIS IN ACUTE STROKE

Stroke, Ischemic Clinical Trial

— NAC-S  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04920448
• Other study ID #: 20-079
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 7, 2021
• Est. completion date: September 7, 2022

Study information

• Verified date: June 2021
• Source: University Hospital, Caen
• Contact: Marion Boulanger, MD, PhD
• Phone: +33231064617
• Email: boulanger-ma[@]chu-caen.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 19
• Est. completion date: September 7, 2022
• Est. primary completion date: June 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 86 Years

Eligibility

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.

Related Conditions & MeSH terms

• Stroke
• Stroke, Ischemic

Intervention

Drug:
• N-Acetyl cysteine
Administered as specified in the treatment arm

Locations

Country	Name	City	State
France	CHU Caen	Caen	Normandy

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

Country where clinical trial is conducted

France, 

References & Publications (1)

Martinez de Lizarrondo S, Gakuba C, Herbig BA, Repessé Y, Ali C, Denis CV, Lenting PJ, Touzé 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Extracranial hemorrhagic events	Rate of extracranial hemorrhagic events	Up to 3 months after treatment
Secondary	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
Secondary	Mortality and functional independence	Rate of mortality and functional independence at 3 months according to the modified Rankin scale (mRs)	3 months after treatment
Secondary	Early neurological improvement	Rate of early neurological improvement defined as an improvement of >4 NIHSS points 24 hours after treatment.	24 hours after treatment
Secondary	Plasma VWF multimers	Mean size of VWF multimers before and after treatment	Before, at 3 hours and at 24 hours after treatment