StrokePhase 3EUREKANCT01364220
The Effects of Very Early Use of Rosuvastatin in Preventing Recurrence of Ischemic Stroke
A Phase 3 study testing Rosuvastatin in people with Stroke, run by Severance Hospital at 27 sites in South Korea.
Trial summary
It is anticipated that 548 subjects will be recruited from approximately 27 centres in South Korea. This is an investigator-sponsored, double-blind, placebo-controlled, randomized, multi-centre study to assess the effects of rosuvastatin 20 mg compared to placebo in acute ischemic stroke patients, with the first dose… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Rosuvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 318 participants
- Where
- 27 sitesSouth Korea
- Study dates
- Aug 2010to Apr 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female over 20 years of age
- Ischemic stroke patients who were undertaken MRI within 48 hrs after onset of symptoms
- Patients underwent baseline MRI (DWI, FLAIR, GRE and MRA)
- Ischemic stroke patients with any degree of stenosis on the relevant artery of atherothrombotic origin appearing on DWI through MRA or CTA
- Statin-naïve (untreated with statin for the past 3 months)
Who cannot join
- Hemorrhagic stroke/ history of symptomatic hemorrhagic stroke.
- Presence of high-risk potential cardiac sources of embolism based on the TOAST classification or other determined etiology of stroke at the time of enrollment.
- Known major hematologic, neoplastic, metabolic, gastrointestinal or endocrine dysfunction which, in the judgment of the Investigator, may affect the subject's ability to complete the study.
- History of malignancy, except in subjects who have been disease-free >5 years or whose only malignancy has been basal or squamous cell skin carcinoma.
- Life-threatening illness indicating the subject is not expected to survive for at least 2 years.
- Secondary causes of nephrotic syndrome, and/or renal dysfunction (serum creatinine >2.0 mg/dL [177 mmol/L]) at screening.
Show all 24Show fewer
- Significant medical or psychological condition that, in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study.
- Unreliability as a study participant based on the Investigator's knowledge of the subject, such as drug or alcohol abuse.
- Pregnant or lactating women or women of childbearing potential who were not protected from pregnancy by an accepted method of contraception, such as the oral contraceptive pill, an intrauterine device or surgical sterilization
- Uncontrolled hypertension defined as either a resting diastolic blood pressure of >110 mmHg or a resting systolic blood pressure of >185 mmHg recorded at screening despite blood pressure lowering therapy.
- Clinically significant heart disease which, in the opinion of the Principal Investigator (or designee), is likely to require coronary bypass surgery, cardiac transplantation, surgical repair and/or replacement during the course of the study.
- Subjects who have symptoms consistent with moderate or greater severity of] congestive heart failure (CHF) (New York Heart Association [NYHA] Class III or IV), or whose most recent determination of left ventricular ejection fraction (LVEF) is <0.35.
- Triglyceride (TG) level of greater than 500 mg/dL at screening.
- LDL level of greater than 190 mg/dL at screening.
- Creatine kinase (CK) >3 times the upper limit of the normal (ULN) range at screening, because of the potential of statins to cause muscle abnormalities.
- Active liver disease or hepatic dysfunction, as determined by aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]) or bilirubin levels >3 x ULN at screening, because of the potential of statins to cause disturbances in liver function.
- Uncontrolled primary hypothyroidism (defined as thyroid stimulating hormone [TSH] >1.5 x ULN.
- Modified Rankin scale score 4 to 6 before stroke.
- Participation in any investigational clinical study for drug or device within 30 days prior to study entry or expectation to participate in any other investigational clinical study for drug or device during the course of this study.
- Patients who may need conventional angiography or intervention within 14 days after enrollment.
- Known serious hypersensitivity reactions to HMG-CoA reductase inhibitors.
- Use of any medication listed in the Prohibited Medications Section
- History of myopathy.
- Patients who has Galactose intolerance,lactose intolerance,Glucose- Galactose absorption problem.
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
South Korea27 sites
Department of Neurology, Hallym University Sacred Heart Hospital
Anyang
Department of Neurology Colleage of Medicine Dong-A University
Busan
Department of Neurology Pusan National University Hospital
Busan
Department of Neurology, College of Medicine Inje University, Paik Hospital
Busan
Department of Neurology, Fatima hospital
Changwon
Department of Neurology, Samsung Changwon hospital
Changwon
Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine
Daegu
Department of Neurology, Yeungnam University School of Medicine
Daegu
Department of Neurology Konyang University Hospital
Daejeon
Department of Neurology, Chonnam National University Hospital
Gwangju
Department of Neurology, Chosun University Hospital
Gwangju
Department of Neurology, Inha University Hospital
Incheon
Department of Neurology, National health insurance corporation ilsan Hospital
Koyang-shi
Department of Neurology, Severance Hospital
Seoul, 120-752
Department of Neurology Gangnam Severance Hospital
Seoul
Department of Neurology Kyung Hee University East-West Neo Medical Center
Seoul
Department of Neurology Seoul National University Hospital
Seoul
Department of Neurology St. Mary's Hospital, Catholic University
Seoul
Department of Neurology, Ewha Womans University Hospital
Seoul
Department of Neurology, Hallym University Medical Center
Seoul
Department of Neurology, Korean University Guro hospital
Seoul
Department of Neurology, Kyung Hee University, College of Medicine
Seoul
Department of Neurology, National Medical Center
Seoul
Department of Neurology, Samsung Medical Center
Seoul
Department of Neurology, University of Ulsan,Asan Medical Center
Seoul
Department of Neurology,Sanggye Paik Hospital, Inje University College of Medicine
Seoul
Department of Neurology, Wonju Christian Hospital
Wŏnju
About this study
Official title: An Investigator-Sponsored,Double Blind,Placebo-controlled,Randomised,Multi-centre Study to Assess the Effects of Very Early Use of Rosuvastatin in Preventing Recurrence of Ischemic Stroke
It is anticipated that 548 subjects will be recruited from approximately 27 centres in South Korea.
This is an investigator-sponsored, double-blind, placebo-controlled, randomized, multi-centre study to assess the effects of rosuvastatin 20 mg compared to placebo in acute ischemic stroke patients, with the first dose within 18 hours after baseline MRI and continued treatment for 14 days.
Read more
Subjects will be male or female, over 20 years, with diagnosis of acute ischemic stroke with baseline MRI, and who are either statin-naïve or untreated with statin for the previous 3 months.
The objective would be to compare the recurrence rate of ischemic stroke by comparing the imaging parameters during 14 days of treatment and clinical improvement as defined by percent improvement based on NIHSS scores measurements at baseline, 5 days and 14 days of treatment.
Read the detailed description
Statins have action mechanisms that may work nicely in preventing recurrence during acute stage of infarction!
First, statins have antithrombotic effects and lower thrombogenicity. Statins prolong time to arterial thrombosis in endothelial injury model, inhibit P-selectin expression and platelet aggregation, reduce platelet PAR-1 thrombin receptor, and reduce tissue factor levels in plasma, its expression on monocyte surface, and atherosclerotic plaques. Second, statins enhance thrombolysis. They reduce PAI-1, increase t-PA activity and reduce fibrinogen level. Combined treatment of statins and t-PA in rats reduces the infarct size and downregulates expression of tissue factor, ICAM-1, vWF, and MMP-9. In addition, t-PA induced toxicity is reversed by statins.
Third, statins have anti-inflammatory actions that can stabilize and even regress plaques. Statins reduce the number of T-lymphocytes within plaques, inhibit migration and activation of monocyte/macrophage system, and reduce matrix metalloproteinase activity that play a critical role in plaque rupture. Rosuvastatin 40 mg could regress coronary atheroma burden at 2 years, and reduce progression of carotid intima-media thickness.
Benefits of statins in stroke patients are partially proven!
First, statins are well known to be effective in primary prevention of stroke. Second, statins were effective in secondary prevention of stroke. A high dose of statin (atorvastatin 80 mg) reduced recurrent stroke in patients with recent TIA or ischemic stroke when it was administrated 1-6 months after stroke onset. However, it is uncertain whether statins are effective during the first month after stroke. Third, outcomes are better in patients under statin treatment at the moment of stroke. Patients pretreated with statins showed better survival, less severe neurologic deficits, and improved outcomes when they were treated with thrombolysis.
However, it is unknown whether statin treatment in stroke patients is effective when it is administrated during the acute stage.
Based on strong supportive evidence in human and experimental animals which support theoretical superiority of rosuvastatin, this study will test a hypothesis that a high dose of rosuvastatin is effective in preventing recurrence during the first month after onset in ischemic stroke patients and should be given to all patients from their onset.
- Conditions
- Stroke
- Being tested
- Rosuvastatin, Placebo tablet
- Keywords
- Additional relevant MeSH terms, Stroke, Cerebral Infarction, Cerebrovascular Disorders, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Magnetic Resonance Imaging, Recurrence
- Medical subject headings
- Stroke, Cerebral Infarction, Cerebrovascular Disorders, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RosuvastatinDrug
Also called Crestor 20mg
Rosuvastatin 20mg tablet, once daily, for 14 days
Placebo tabletOther
Placebo tablet, once daily, for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Rosuvastatin | Experimental | Rosuvastatin 20mg tablet, once daily, for 14 days Receives: Drug: Rosuvastatin |
| Placebo | Placebo comparator | Placebo tablet, once daily, for 14 days Receives: Other: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence Of Newly Developed DWI Lesions
The objective would be to Compare the recurrence rate of ischemic strike by comparing the PRESENCE of newly developed DWI between baseline and after 14 days of treatment.
Measured: During 14 days of treatment
Secondary outcomes (1)
Volume Of DWI Lesions With Percent Improvement Of NIHSS Score
- Percent Improvement Based On NIHSS Score Measurements At Baseline, 5 Days And 14 Days Of Treatment.
- Volume Of DWI Lesions
Measured: During 14 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study startAug 2010
- Primary completionApr 2013
- Study completionApr 2013
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- Severance Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Ji Hoe Heo, Severance Hospital
- Investigators
- Ji Hoe Heo, MD., Ph. D, Principal investigator, Department of Neurology, Severance Hospital, 250 Seongsan-no,Seodaemun-gu,Seoul,120-752, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01364220
- Sponsor's protocol ID
- D3560L00087
- Acronym
- EUREKA
- Status last verified
- Nov 2014
- First submitted
- 26 May 2011
- Last updated
- 20 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-Sponsored,Double Blind,Placebo-controlled,Randomised,Multi-centre Study to Assess the Effects of Very Early Use of Rosuvastatin in Preventing Recurrence of Ischemic Stroke
- ClinicalTrials.gov ID
- NCT01364220
- Acronym / sponsor ID
- EUREKA / D3560L00087
- Conditions
- Stroke
- Keywords
- Additional relevant MeSH terms, Stroke, Cerebral Infarction, Cerebrovascular Disorders, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Magnetic Resonance Imaging, Recurrence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 318 participants (actual)
- Lead sponsor
- Severance HospitalUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Aug 2010
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is anticipated that 548 subjects will be recruited from approximately 27 centres in South Korea.
This is an investigator-sponsored, double-blind, placebo-controlled, randomized, multi-centre study to assess the effects of rosuvastatin 20 mg compared to placebo in acute ischemic stroke patients, with the first dose within 18 hours after baseline MRI and continued treatment for 14 days.
Subjects will be male or female, over 20 years, with diagnosis of acute ischemic stroke with baseline MRI, and who are either statin-naïve or untreated with statin for the previous 3 months.
The objective would be to compare the recurrence rate of ischemic stroke by comparing the imaging parameters during 14 days of treatment and clinical improvement as defined by percent improvement based on NIHSS scores measurements at baseline, 5 days and 14 days of treatment.
Detailed description
Statins have action mechanisms that may work nicely in preventing recurrence during acute stage of infarction!
First, statins have antithrombotic effects and lower thrombogenicity. Statins prolong time to arterial thrombosis in endothelial injury model, inhibit P-selectin expression and platelet aggregation, reduce platelet PAR-1 thrombin receptor, and reduce tissue factor levels in plasma, its expression on monocyte surface, and atherosclerotic plaques. Second, statins enhance thrombolysis. They reduce PAI-1, increase t-PA activity and reduce fibrinogen level. Combined treatment of statins and t-PA in rats reduces the infarct size and downregulates expression of tissue factor, ICAM-1, vWF, and MMP-9. In addition, t-PA induced toxicity is reversed by statins.
Third, statins have anti-inflammatory actions that can stabilize and even regress plaques. Statins reduce the number of T-lymphocytes within plaques, inhibit migration and activation of monocyte/macrophage system, and reduce matrix metalloproteinase activity that play a critical role in plaque rupture. Rosuvastatin 40 mg could regress coronary atheroma burden at 2 years, and reduce progression of carotid intima-media thickness.
Benefits of statins in stroke patients are partially proven!
First, statins are well known to be effective in primary prevention of stroke. Second, statins were effective in secondary prevention of stroke. A high dose of statin (atorvastatin 80 mg) reduced recurrent stroke in patients with recent TIA or ischemic stroke when it was administrated 1-6 months after stroke onset. However, it is uncertain whether statins are effective during the first month after stroke. Third, outcomes are better in patients under statin treatment at the moment of stroke. Patients pretreated with statins showed better survival, less severe neurologic deficits, and improved outcomes when they were treated with thrombolysis.
However, it is unknown whether statin treatment in stroke patients is effective when it is administrated during the acute stage.
Based on strong supportive evidence in human and experimental animals which support theoretical superiority of rosuvastatin, this study will test a hypothesis that a high dose of rosuvastatin is effective in preventing recurrence during the first month after onset in ischemic stroke patients and should be given to all patients from their onset.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rosuvastatin | Experimental | Drug: RosuvastatinRosuvastatin 20mg tablet, once daily, for 14 days |
| Placebo | Placebo comparator | Other: Placebo tabletPlacebo tablet, once daily, for 14 days |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female over 20 years of age
- Ischemic stroke patients who were undertaken MRI within 48 hrs after onset of symptoms
- Patients underwent baseline MRI (DWI, FLAIR, GRE and MRA)
- Ischemic stroke patients with any degree of stenosis on the relevant artery of atherothrombotic origin appearing on DWI through MRA or CTA
- Statin-naïve (untreated with statin for the past 3 months)
Key exclusion criteria (24 listed)
- Hemorrhagic stroke/ history of symptomatic hemorrhagic stroke.
- Presence of high-risk potential cardiac sources of embolism based on the TOAST classification or other determined etiology of stroke at the time of enrollment.
- Known major hematologic, neoplastic, metabolic, gastrointestinal or endocrine dysfunction which, in the judgment of the Investigator, may affect the subject's ability to complete the study.
- History of malignancy, except in subjects who have been disease-free >5 years or whose only malignancy has been basal or squamous cell skin carcinoma.
- Life-threatening illness indicating the subject is not expected to survive for at least 2 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RosuvastatinAlso: Crestor 20mgRosuvastatin 20mg tablet, once daily, for 14 days | Drug | Rosuvastatin |
| Placebo tabletPlacebo tablet, once daily, for 14 days | Other | Placebo |
Primary outcome
Presence Of Newly Developed DWI Lesions
Time frame: During 14 days of treatment
The objective would be to Compare the recurrence rate of ischemic strike by comparing the PRESENCE of newly developed DWI between baseline and after 14 days of treatment.
1 secondary outcome
Volume Of DWI Lesions With Percent Improvement Of NIHSS Score
Time frame: During 14 days of treatment
Results and safety
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ji Hoe Heo, MD., Ph. D principal investigator
Department of Neurology, Severance Hospital, 250 Seongsan-no,Seodaemun-gu,Seoul,120-752, Korea
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rosuvastatin in people with Stroke, run by Severance Hospital at 27 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence Of Newly Developed DWI Lesions (time frame: During 14 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2014.