Intensive Rosuvastatin Therapy on Cerebral Hemodynamics in Patients With Atherosclerotic Intracranial Arterial Stenosis

Atherosclerosis Clinical Trial

Official title:

The Impact of Intensive Rosuvastatin Therapy on Cerebral Hemodynamics in Patients With Atherosclerotic Intracranial Arterial Stenosis Evaluated by Computed Tomography Perfusion (CTP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02594800
• Other study ID #: ESR-14-10688
• Status: Completed
• Phase: Phase 4
• Start date: December 21, 2015
• Est. completion date: June 30, 2019

Study information

• Verified date: June 2019
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atherosclerotic intracranial arterial stenosis (AICAS) corresponds to luminal narrowing of the major intracranial arteries. The prevalence of intracranial atherosclerotic stenosis accounts for 33% to 67% of stroke or transient ischemic attack (TIA) cases in China and other countries in Asia. AICAS is also highly associated with the risk of stroke recurrence. Possible mechanisms of cerebral infarction secondary to AICAS are likely linked with hemodynamic compromise distal to site of stenosis.

Computed tomography perfusion (CTP) can be used to evaluate vasoreactivity and cerebrovascular reserve in patients with AICAS and predict future stroke. The parameters of CTP include ①cerebral blood flow(CBF),② cerebral blood volume(CBV) and ③mean transit time(MTT). Relative regional cerebral blood flow (rCBF) was evaluated as the percentage radioisotope counts in the region of interest (ROI) of the affected side against the corresponding ROI in the unaffected contralateral side.

Statins can decrease the incidence of transient ischemic attack or ischemic stroke and improve stroke outcome. Few studies focus on the relationship between statins therapy and cerebral perfusion.

Whether intensive rosuvastatin therapy compared with standard rosuvastatin therapy can improve hemodynamic situation and cerebral perfusion status in AICAS has not been illustrated.

Based on those studies, the investigators hypothesized that intensive rosuvastatin may also improve the symptoms of AICAS not only through enhancing the stability of atherosclerotic plaques, but also its pleiotropic effects. So it can change the hemodynamic status around the plaque and increase cerebral flow in the downstream territory. So in this study the investigators try to analysis statin's impact on the hemodynamic changes as well as the downstream perfusion which is determined by CTP.

Description:

This is an prospective, randomized, single-blind, single center clinical trial to evaluate the effect of intensive rosuvastatin therapy compared with standard rosuvastatin therapy on improve the cerebral perfusion in Chinese patients with atherosclerotic intracranial arterial stenosis between 50-99%.

The study will enroll 44 patients and randomly divided into 2 groups: standard dose rosuvastatin therapy (SRT 10mg/day)and intensive dose rosuvastatin therapy (IRT 20mg/day)in a 1:1 ratio. Both groups will be prescribed with statin based on other routine medication for stroke for 52 weeks. CTP will be performed at baseline and 52 weeks after treatment. Lipid levels and biochemical examinations will be obtained at baseline and 13, 26, 39, 52 week. AEs(Adverse Events)/SAEs(Serious Adverse Events) will be collected and recorded in CRF(Case Report Form) from the signing of informed consent throughout the study until and including the last visit.

Study Endpoints: Primary endpoint: Compared with standard dose rosuvastatin therapy 10mg/day, the change of relative cerebral blood flow (CBF) by CTP after intensive dose rosuvastatin therapy 20mg/day treatment for 52 weeks.Secondary endpoints: (1) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of relative cerebral blood volume (CBV) by CTP after rosuvastatin 20mg/d treatment for 52 weeks (2) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of relative mean transit time (MTT) by CTP after rosuvastatin 20mg/d treatment for 52 weeks (3) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of lipid parameters (LDL-C, HDL-C, TG(Triglyceride), TC(Total Cholesterol), Apo A and Apo B ) after rosuvastatin 20mg/d for 52 weeks (4) Safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 30, 2019
• Est. primary completion date: July 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Provision of informed consent

2. Male and female adults aged 18-80years old

3. Recent (within 3 months) ischemic stroke or TIA;

4. Intracranial large artery (intracranial internal artery, middle cerebral artery M1, vertebral artery and basilar artery) stenosis between 50-99%.

5. Statin naïve:defined as receiving no statin therapy within 3 months

Exclusion Criteria:

1. Cardioembolic stroke;

2. Rosuvastatin use is contraindicated;

3. Allergic to contrast agents;

4. Chronic devastating illness, multiple organ failure;

5. Dementia or mental disorder unable to return for repeat brain CTP.

6. Administration of lipid-lowering drugs (statin, clofibrate, probucol or analog, nicotinic acid, or other prohibited drug) before enrollment.

7. Active liver disease or aminopherase ?3 ULN(Upper Limit of Normal)

8. Renal function damage. GFR(Glomerular Filtration Rate) ?30ml/min

Related Conditions & MeSH terms

• Atherosclerosis
• Constriction, Pathologic

Intervention

Drug:
• Rosuvastatin
standard or intensive dose rosuvastatin therapy based on other routine medication for stroke for 52 weeks.

Locations

Country	Name	City	State
China	The second affiliated hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the change of relative cerebral blood flow (CBF) (ml/100g/min)by CTP		52 weeks
Secondary	the changes of relative cerebral blood volume (CBV)(ml/100g) by CTP		52 weeks
Secondary	the changes of relative mean transit time (MTT)(min) by CTP		52 weeks
Secondary	the changes of lipid parameters (LDL-C,mmol/L;HDL-C,mmol/L;TG,mmol/L;TC,mmol/L;Apo A,mmol/L;Apo B,mmol/L )		13, 26, 39, 52 week
Secondary	myopathic events, hepatic function, renal function and other adverse events.		52 weeks