StrokeSEATISNCT02452502
The Safety and Efficacy Study of High Dose Atorvastatin After Thrombolytic Treatment in Acute Ischemic Stroke
A study testing atorvastatin in people with Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 2 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- atorvastatin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 254 participants
- Where
- 2 sitesChina
- Study dates
- 2 Sep 2015to Aug 2018
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.:
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- 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
Trial locations and contacts
2 sites in 1 country.
China2 sites
Jilin First Hospital
Changchun, Jilin
Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
About this study
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.
Read more
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.
Read the detailed description
Study design It is a bi-center, randomized, open-label prospective study. Investigators will enroll the ischemic stroke patients who received IV-thrombolysis with rt-PA. Those who meet inclusion criteria will be randomized either to the high dose group (atorvastatin 80mg) or the moderate dose group (atorvastatin 20mg) within 24 hours after IVT. The initial dose of atorvastatin will last at least 2 weeks, and then be adjusted according to the stroke risk stratification and tolerance. All patients will be followed at 0, 1 month, 3 months, 6 months, and 12 months, and evaluated the neurological deficits and some patients will be randomly assigned to perform multimodality MRI scan. Other standard secondary prevention of stroke and life-style guidance will be provided according to 2014 AHA/ASA stroke secondary prevention guidelines. All patients will be followed up in stroke prevention clinic or on phone by trained investigators.
Study Endpoints Primary endpoint 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.
Secondary endpoints NIHSS score at 7 day, 1 month mRS at 6,12 month Inflammation biomarkers at 6 month Imaging outcomes include the neuronal and vascular morphological changes indicated by multi-model imaging.
Safety and tolerability will be evaluated by recording the incidence and severity of adverse events, abnormal physical examination findings, and abnormal laboratory values through the study. Especially monitoring the patients who have any the following events:
Hemorrhagic complications including intracranial, digestive tract. New stroke or TIA Death from all-cause death, stroke events or cardiovascular events The patients having muscle symptoms such as myalgia, fatigue, weakness, creatinine kinase values 10 times the upper limit of normal, or rhabdomyolysis, and having persistent elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or both (defined as two consecutive measurements obtained 4 to 10 days apart that is more than three times the upper limit of the normal range).
- Conditions
- Stroke
- Being tested
- atorvastatin
- Keywords
- stroke, thrombolytic therapy, atorvastatin
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatinDevice
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Device: atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (5)
NIHSS score at 7 day, 1 month
Measured: 7 day, 1 month
mRS at 6,12 month
Measured: 6 months, 12 months
Hemorrhagic complications including intracranial, digestive tract
Measured: 6 months, 12 months
New stroke or TIA
Measured: 12 months
Death from all-cause death, stroke events or cardiovascular events
Measured: 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study start2 Sep 2015
- Primary completionNov 2017
- Study completionAug 2018
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.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 254 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The First Hospital of Jilin University
- Responsible party
- Principal investigator, Min Lou, Second Affiliated Hospital, Zhejiang University, School of Medicine
- Investigators
- Min Lou, Ph.D, Principal investigator, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02452502
- Sponsor's protocol ID
- LOU52256
- Acronym
- SEATIS
- Status last verified
- Mar 2020
- First submitted
- 20 May 2015
- Last updated
- 31 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy Study of High Dose Atorvastatin After Thrombolytic Treatment in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT02452502
- Acronym / sponsor ID
- SEATIS / LOU52256
- Conditions
- Stroke
- Keywords
- stroke, thrombolytic therapy, atorvastatin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- The First Hospital of Jilin University
- Study start
- 2 Sep 2015 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 22 May 2015 (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.
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.
Detailed description
Study design It is a bi-center, randomized, open-label prospective study. Investigators will enroll the ischemic stroke patients who received IV-thrombolysis with rt-PA. Those who meet inclusion criteria will be randomized either to the high dose group (atorvastatin 80mg) or the moderate dose group (atorvastatin 20mg) within 24 hours after IVT. The initial dose of atorvastatin will last at least 2 weeks, and then be adjusted according to the stroke risk stratification and tolerance. All patients will be followed at 0, 1 month, 3 months, 6 months, and 12 months, and evaluated the neurological deficits and some patients will be randomly assigned to perform multimodality MRI scan. Other standard secondary prevention of stroke and life-style guidance will be provided according to 2014 AHA/ASA stroke secondary prevention guidelines. All patients will be followed up in stroke prevention clinic or on phone by trained investigators.
Study Endpoints Primary endpoint 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.
Secondary endpoints NIHSS score at 7 day, 1 month mRS at 6,12 month Inflammation biomarkers at 6 month Imaging outcomes include the neuronal and vascular morphological changes indicated by multi-model imaging.
Safety and tolerability will be evaluated by recording the incidence and severity of adverse events, abnormal physical examination findings, and abnormal laboratory values through the study. Especially monitoring the patients who have any the following events:
Hemorrhagic complications including intracranial, digestive tract. New stroke or TIA Death from all-cause death, stroke events or cardiovascular events The patients having muscle symptoms such as myalgia, fatigue, weakness, creatinine kinase values 10 times the upper limit of normal, or rhabdomyolysis, and having persistent elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or both (defined as two consecutive measurements obtained 4 to 10 days apart that is more than three times the upper limit of the normal range).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| moderate dose | Active comparator | Device: atorvastatinDrug: 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 |
| high dose | Experimental | Device: atorvastatinDrug: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| atorvastatinAtorvastatin 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 | Device | high dose, moderate dose |
Primary outcome
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.
Time frame: 90 days
5 secondary outcomes
NIHSS score at 7 day, 1 month
Time frame: 7 day, 1 month
mRS at 6,12 month
Time frame: 6 months, 12 months
Hemorrhagic complications including intracranial, digestive tract
Time frame: 6 months, 12 months
New stroke or TIA
Time frame: 12 months
Death from all-cause death, stroke events or cardiovascular events
Time frame: 6 months, 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
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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.
Min Lou, Ph.D principal investigator
Second Affiliated Hospital, Zhejiang University, School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing atorvastatin in people with Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 2 sites in China.
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 6 inclusion and 10 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: finished, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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. (time frame: 90 days). 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 31 Mar 2020.