Clinical trial NCT02484027: Effect of Rosuvastatin on Prognosis of Clinical Response in Acute Ischemic Stroke Patients(REPAIRS)
Official title: Effect of Rosuvastatin on Prognosis of Clinical Response in Acute Ischemic Stroke Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Infarction, Anterior Cerebral Artery
Keywords: acute ischemic stroke
mRS
rosuvastatin
Lead sponsor: Second Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Taicang No.1 People's hospital
name: AstraZeneca
name: National Natural Science Foundation of China
First posted: 2015-06-29
Enrollment: 456
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is randomized, open-lable, parallel-group and comparator-controlled. 456 consecutive patients with acute ischemic stroke admitted within the first 72 hours after onset of symptoms will be studied. Those patients who will be randomly assigned to receive 2 different treatment for the first 3 days of hospitalization(non-statin-therapy group) or to immediately receive rosuvastatin orally at a dose of 20mg daily (statin-therapy group). From the fourth day onward, rosuvastatin 10 mg daily will be administered in all patients. The total trial will be continued 12 months.

mRS will be investigated at baseline, 3rd month, 12th month ;MMSE and Montreal tests will be investigated at baseline and 12th month. Laboratory data including serum lipids, Fg and hs-CRP.Among these, serum lipids will be tested at baseline, 8th day, 3rd month, 6th month,and 12th month; hs-CRP will be tested at baseline and 8th day, 3rd month; Fg will be tested at baseline, 8th day, 3rd month. Safety will be also assessed by adverse event reports and clinical laboratory data including CK-MB, renal and hepatic function at 3rd month, 6th month,12th month.

Detailed description: This study is randomized, open-lable, parallel-group and comparator-controlled.456 consecutive patients with anterior circulation ischemic stroke within 72h from 2 participating hospitals are enrolled into the study. Those patients who will be randomly assigned to receive 2 different treatments for the first 3 days of hospitalization(non-statin-therapy group) or to immediately receive rosuvastatin orally at a dose of 20mg daily (statin-therapy group). From the fourth day onward, rosuvastatin 10 mg daily will be administered in all patients. The total trial will be continued 12 months.Subject eligibility will be established before treatment randomization. A random number table will be generated using a computerized procedure and subjects will be randomized strictly sequentially as they are eligible for randomization. The randomization procedure will be done like this. The random number will be divided by 2. And if the remainder is 1, the subject will be assigned to intensive rosuvastatin group. Correspondingly, if the remainder is 0, the subject will be assigned to the non-rosuvastatin group. Subjects will be randomized on a 1:1 schedule.

According to the previous post hoc analysis and SPARCL analysis results, the mRS event rate (mRS\>2) at 90 days among statin-naïve patients before admission is 42% without statin treatment in the first 3 days of admission versus 28% with statin immediately used since admission. Previous studies showed there is benefit with statin treatment in the earlier period of acute ischemic stroke, so the data from SPARCL reserved conservatively because the patients within 6 months of stroke onset were enrolled. It is based on these reported event rates, a sample size of 182 patients per group will have 80% power to detect a rate difference of 14%, assuming a null rate difference of zero and using Pearson's chi-squared test with a two-sided significance level of 0.05. With an estimated 20% rate of dropping out from the study, a total of 456 patients will have to be randomized (228 in each group) for this study.

Medical histories were obtained from all subjects before enrollment. Patients are followed by 1 year. mRS will be investigated at baseline, 3rd month, 12th month ;MMSE and Montreal tests will be investigated at baseline and 12th month. Laboratory data include serum lipids, Fg and hs-CRP.Among these, serum lipids will be tested at baseline, 8th day and 3rd month, 6th month,12th month; hs-CRP will be tested at baseline and 8th day, 3rd month, Fg will be tested at baseline, 8th day, 3rd month. Safety will be also assessed by adverse event reports and clinical laboratory data including CK-MB, renal and hepatic function at 3rd month, 6th month,12th month.

Primary endpoint is the proportion of poor prognosis(modified Rankin scores\>2) at 3 and 12 months post discharge. mRS scores\>2 is defined as poor prognosis. And mRS scores≤2 scores were defined as good prognosis. Primary endpoint is the comparison of percentage of poor prognosis between two groups. Second endpoints include change from baseline in serum lipid, Fg and hs-CRP levels at 8th day, 3rd month, 6th month and 12th month after randomization. The incidence of vascular endpoint events including all-cause mortality, any event of recurrent ischemic stroke/TIA, hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. And change from admission in MMSE and Montreal scores of all subjects at 12th month.

Researchers who are responsible for evaluation of mRS, NIHSS scores, MMSE and Montreal scores will receive centralized training and be specialized. Specialized doctors follow-up the subjects with no knowledge of the statin therapies for the patients. Every month a meeting will be held to know if there are problems and to solve them.

Two special doctors in each center are responsible for follow-up visits. Patients will be asked to bring all empty packages to the clinic at each visit. The patient's compliance will be assessed by the investigator and recorded in the CRF. A pill count should be done at a patient level and recorded in the CRF and a dispensing log by the study site personnel.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Adults between 35 and 80 years old
3. Anterior circulation ischemic stroke within 72h of large arterial atherosclerosis subtype
4. First attack or without obvious sequelae after previous attacks of stroke(mRS≤1)
5. NIHSS score less than 24 when onset
6. Statin-naive(no statin therapy in the past 3 months)

Exclusion Criteria:

1. Familial hypercholesterolemia
2. Cardiogenic embolism and hemorrhagic transformation
3. Unknown cause and rare cause stroke subtypes
4. On or need to be on anticoagulant therapy
5. Severe hepatic(e.g. active liver disease, ALT or AST over 3 times of ULN), renal, hematopoietic, endocrine, myopathy , mental and cognitive diseases
6. Subjects with thrombolytic therapy
7. Concomitant treatment with ciclosporin
8. Allergy to statins or antiplatelet drugs
9. Planning to have a major operation or carotid ,vertebral angioplasty
10. Pregnancy and poor compliance.

Primary outcomes:
measure: proportion of patients with poor prognosis(modified Rankin scale>2)
timeFrame: 3rd month after onset of stroke
measure: proportion of patients with poor prognosis(modified Rankin scale>2)
timeFrame: 12th month after onset of stroke
Secondary outcomes:
measure: the occurrence of vascular events( a composite)
timeFrame: 12th months after onset of stroke
measure: Change from baseline in cognitive function at 12 months
timeFrame: 12 months
Other outcomes:
measure: Change from baseline in serum lipids(a composite) at 12 months
timeFrame: 3rd, 8th day and 3 rd, 6th and 12th month
measure: Change from baseline in hs-CRP level at 3 months
timeFrame: baseline, 3rd, 6th and 12th month
measure: Change from baseline in Fg level at 3 months
timeFrame: 3rd month
measure: Incidence of abnormal hepatic function(a composite)
timeFrame: 3rd month
measure: Incidence of abnormal hepatic function(a composite)
timeFrame: 12th month
measure: Incidence of renal dysfunction
timeFrame: 3rd month
measure: Incidence of renal dysfunction
timeFrame: 12th month
measure: Incidence of elevation of serum CK levels
timeFrame: 3rd month
measure: Incidence of elevation of serum CK levels
timeFrame: 12th month
Locations:
city: Suzhou
country: China
facility: Department of Neurology, Second Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: Second Afflilated Hospital of Soochow University
name: Chun-Feng Liu, Ph.D,M.D.
role: STUDY_CHAIR
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