The Safety and Efficacy Study of High Dose Atorvastatin After Thrombolytic Treatment in Acute Ischemic Stroke

NCT02452502 | Completed DMC

• 1 other identifier: LOU52256
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 2

Brief Summary

Emerging studies have shown that statin treatment has pleiotropic non-cholesterol-dependent effects in the setting of ischemic stroke. Recombinant tissue plasminogen activator (rt-PA) is the only proven effective pharmaceutical treatment for hyper-acute management of ischemic stroke, in spite of the deleterious side-effects such as hemorrhagic transformation and reperfusion injury. These harmful impacts can be counteracted with proper neuro-protective therapy. In fact, the simultaneous use of an effective neuro-protective agent was proved to reduce the comorbid vascular injury of rt-PA. In experimental research, high dose of atorvastatin combined with rt-PA can significantly reduce infarct volume and improve the neurologic deficits. Previous studies showed that fewer than 40% ischemic stroke patients established early reperfusion after intravenous thrombolysis, while high dose of atorvastatin was revealed to favor the maintenance of cerebral vascular patency and integrity, most likely by reducing thrombosis secondary to rt-PA administration. Moreover, it was suggested that statin can sufficiently improve the restoration and remodeling of neurovascular unit in cerebral cortex. Investigators thus design this study to prospectively investigate whether high dose of atorvastatin prescribed within 24 hours after IV-thrombolysis will have a synergic effect to improve neurological outcome in acute ischemic stroke patients. Moreover, investigators deemed it necessary to non-invasively monitor neuronal and vascular morphological changes in brain as an indication of functional improvement. In the investigation centers, investigators have developed and implemented novel multimodality MR imaging which can dynamically monitor neurovascular remodeling. Therefore, it is worthwhile to evaluate these MRI measurements for early prediction of neurovascular reorganization with long term functional recovery in thrombolytic stroke patients administrated with high dose of atorvastatin. The primary target of this study is to prospectively investigate whether high dose of atorvastatin (80mg) administrated within 24 hours after IV-thrombolysis will have a synergic effect to improve neurological outcome in acute stroke patients, versus moderate dose.

Conditions

Stroke

Keywords

stroke; thrombolytic therapy; atorvastatin

Outcome Measures

Primary Outcomes (1)

• The percentage of patients with mRS (modified Rankin Score) equivalent to or less than 2 between high dose groups and moderate dose groups at 90 days.

  90 days

Secondary Outcomes (5)

• NIHSS score at 7 day, 1 month

  7 day, 1 month

• mRS at 6,12 month

  6 months, 12 months

• Hemorrhagic complications including intracranial, digestive tract

  6 months, 12 months

• New stroke or TIA

  12 months

• Death from all-cause death, stroke events or cardiovascular events

  6 months, 12 months

Study Arms (2)

moderate dose

ACTIVE COMPARATOR

Drug: Atorvastatin Atorvastatin 20 mg daily for 2 weeks administrated within 24 hours after receiving rt-PA thrombolysis, continued statin use for at least 12 months Other Name: Lipitor

Device: atorvastatin

high dose

EXPERIMENTAL

Drug: Atorvastatin Atorvastatin 80 mg daily for 2 weeks administrated within 24 hours after receiving rt-PA thrombolysis, continued statin use for at least 12 months Other Name: Lipitor

Device: atorvastatin

Interventions

atorvastatin DEVICE

Atorvastatin high or moderate dose daily for 2 weeks administrated within 24 hours after receiving rt-PA thrombolysis, continued statin use for at least 12 months

high dose; moderate dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≧18 years of age
• Able and willing to comply with study requirements
• Signed informed consent by patient self or legally authorized representatives.
• Baseline mRS before this stroke onset less than 2
• Receive IV rt-PA thrombolysis with a final diagnosis of ischemic stroke
• Liver transaminases (ALT and/or AST) ≤ 2 x upper limit of normal (ULN) with no active liver disease and creatine kinase (CK) ≤ 2 x ULN at screen visit.

You may not qualify if:

• History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy
• Patients who have been treated with any other investigational drug within 3 months of enrollment
• Impaired renal function ( serum creatinine ≧1.5 mg/dL) or nephrotic syndrome
• Patients hypersensitive or have allergic response to HMG-CoA reductase inhibitors
• Metastatic neoplasm at the onset or the follow-up
• Prohibited concomitant therapies, e.g.:
• ① Medications that are potent inhibitors of CYP3A4, including cyclosporine, systemic itraconazole or ketoconazole, erythromycin or clarithromycin, nefazodone, verapamil and human immunodeficiency virus (HIV) protease inhibitors.
• ②Oral corticosteroids unless used as replacement therapy for pituitary/adrenal disease
• Patient has evidence of severe congestive heart failure or has history of end-stage cardiovascular disease (e.g. CHF NYHA Class III or IV)
• Any condition or situation which, in the opinion of the investigator, might pose a risk to the patient or confound the results of the study

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• The First Hospital of Jilin University: collaborator

Study Sites (2)

Jilin First Hospital

Changchun, Jilin, China

Location

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Min Lou, Ph.D

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate director of Neurology Department

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 22, 2015
• Study Start: September 2, 2015
• Primary Completion: November 1, 2017
• Study Completion: August 1, 2018
• Last Updated: March 31, 2020

Record last verified: 2020-03

Locations

CN (2)