Effect of Rosuvastatin on Prognosis of Clinical Response in Acute Ischemic Stroke Patients(REPAIRS)

NCT ID: NCT02484027

Last Updated: 2015-06-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 456 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2018-09-30

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.

Conditions

Infarction, Anterior Cerebral Artery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

statin-therapy

Rosuvastatin orally at a dose of 20mg daily is assigned to patients immediately for the first 3 days of hospitalization. From the fourth day onward, rosuvastatin 10 mg daily will be administered for 1 year.

Group Type: EXPERIMENTAL

Rosuvastatin

Intervention Type: DRUG

Patients will be randomly assigned to receive 2 different therapies for the first 3 days of hospitalization: no statins (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 for 1 year

non-statin-therapy

No statins is assigned to patients for the first 3 days of hospitalization. From the fourth day onward, rosuvastatin 10 mg daily will be administered for 1 year.

Group Type: SHAM_COMPARATOR

Rosuvastatin

Intervention Type: DRUG

Patients will be randomly assigned to receive 2 different therapies for the first 3 days of hospitalization: no statins (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 for 1 year

Interventions

Rosuvastatin

Patients will be randomly assigned to receive 2 different therapies for the first 3 days of hospitalization: no statins (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 for 1 year

Intervention Type: DRUG

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taicang No.1 People's hospital

UNKNOWN

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

National Natural Science Foundation of China

OTHER_GOV

Sponsor Role: collaborator

Second Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Chun-Feng Liu

Associate Dean

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chun-Feng Liu, Ph.D,M.D.

Role: STUDY_CHAIR

Second Afflilated Hospital of Soochow University

Locations

Department of Neurology, Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

Central Contacts

Chun-Feng Liu, Ph.D,M.D.

Role: CONTACT

liucf@suda.edu.cn

00 86 512 67783307

Facility Contacts

Chun-Feng Liu, Ph.D, M.D.

Role: primary

liucf@suda.edu.cn

00 86 512 67783307

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Other Identifiers

ESR-14-10580

Identifier Type: -

Identifier Source: org_study_id