Contact information
Type
Scientific
Primary contact
Prof Yongjun Wang
ORCID ID
Contact details
No.6
Tiantanxili
Chongwen District
Beijing
100050
China
+86 (0)10 67038316
yongjunwang111@yahoo.com.cn
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2004BA714B6
Study information
Scientific title
Acronym
ITAIS
Study hypothesis
Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is an effective therapy for ischemic stroke within 3 hours, but most acute ischemic stroke patients arrive at hospital after the 3-hour time window. To select patients by modern magnetic resonance imaging (MRI) technology may extend this time window. Mismatch between perfusion weighted image (PWI) deficits and diffusion weighted image (DWI) lesions putatively represents the penumbra. Intra-arterial thrombolysis is also a promising therapy for those patients beyond the 3-hour time window. And until now, there is still no strict randomized controlled trial to compare safety and efficacy between intravenous and intra-arterial thrombolysis with rt-PA.
Ethics approval
The protocol has been approved by the Institutional Review Board of the Beijing Tiantan Hospital and other hospitals.
Study design
Prospective multicentre randomised open (assessor-blind) trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Acute ischemic stroke
Intervention
This is a prospective, multicenter, randomized, open, assessor-blind study to assess the efficacy and safety of intra-arterial and intravenous thrombolysis in acute ischemic stroke patients within 3-9 hours time window to use MRI both for patient selection and as a primary efficacy endpoint.
Patients in 3-6 hours time window receive intra-arterial or intravenous thrombolysis with rt-PA randomly. Patients in 6-9 hours time window receive intravenous thrombolysis or conventional therapy randomly. All enrolled patients have standardized DWI, PWI and MRA.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
1. Imaging outcome:
a. Reperfusion was assessed 24 to 48 hours posttreatment and defined as either >=30% reduction of mean transit time (MTT) volume of abnormality or >=2 points improvement on the TICI grading scheme using MRA
b. The change in infarct lesion volume on DWI from baseline to 24 to 48 hours and 21 days
2. Clinical outcome:
a. Global outcome at day 90:
The combined analysis of the NIHSS, modified Rankin scale (mRS), and Barthel Index (BI) defined as ≥8 points improvement or scoring 0 to 1 on the NIHSS, a score of 0 to 2 on mRS, and a BI score of 75 to 100.
Modified Rankin Scale 0-1, Barthel Index ≥95, NIHSS 0-1 (inclusive distal motor function)
b. Disability status at day 90:
mRS 0-2 (independent outcome), Barthel Index >=85
Secondary outcome measures
1. Functional status at day 30:
mRS (total score), median Barthel Index (total score), median NIHSS (total score), mean/median change from baseline NIHSS (8 points improvement or 0-1)
2. Functional status at day 7:
NIHSS (total score), mean/median change from baseline NIHSS (4 points improvement or 0-1)
3. Functional status at 24 to 48 hours:
NIHSS (total score), mean/median change from baseline
4. Functional status at day 0 (1 and 2 hours after treatment):
NIHSS (total score), mean/median change from baseline
5. Stratified endpoint of NIHSS and mRS:
NIHSS <8: mRS 0 response,
8<=NIHSS<=14: mRS 0-1 response, NIHSS >14: mRS 0-2 response
6. Length of stay in hospital
Overall trial start date
01/06/2005
Overall trial end date
01/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 18-75 years
2. Clinical signs consistent with the diagnosis of ischemic stroke
3. Treatment onset within 3-9 hours after stroke onset
4. No prior neurologic event that would obscure the interpretation of the signal
and current presenting neurologic deficits (modified Rankin scale [mRS] ≤1)
5. National Institutes of Health-Stroke-Scale (NIHSS) score >4 and at least moderate limb weakness
6. MRI screening to be started within 7.5 hours after stroke onset
7. Perfusion abnormality of >2 cm in diameter involving hemispheric gray matter
8. Perfusion/diffusion mismatch of ≥20
9. Magnetic resonance angiography (MRA) shows that TICI grade is 0 or 1
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
The planned total number of treated subjects is 80.
Participant exclusion criteria
1. Patients not eligible to receive trial treatment within 30-60 min after completion of MRI1
2. Coma
3. Stroke symptoms are rapidly improving by the time of randomization
4. Major stroke symptoms (>25 to 30 on the NIHSS)
5. History of stroke within the previous 6 weeks
6. Seizure at the onset of stroke
7. Stroke due to a neurointerventional procedure for treatment of a cerebral aneurysm and/or cerebral arteriovenous malformation (stroke due to diagnostic cerebral angiography or cardiac catheterization might be treated)
8. Clinical presentation suggestive of subarachnoid hemorrhage, even when the MRI is normal
9. History of intracerebral hemorrhage (ICH) at any time, neoplasm, subarachnoid hemorrhage (SAH), arteriovenous malformation (AVM) or aneurysm
10. Presumed septic embolus
11. Presumed pericarditis related to recent acute myocardial infarction
12. Recent (within 10 to 30 days) surgery, biopsy of a parenchymal organ, or lumbar puncture
13. Recent (within 10 to 30 days) trauma (including head trauma), with internal injuries or ulcerative wounds
14. Known active inflammatory bowel disease, ulcerative colitis, or diverticular disease
15. Any active or recent (within 10 to 30 days) hemorrhage
16. Known hereditary or acquired hemorrhagic diathesis. Baseline laboratory values that reveal platelets are <100 000/µl, hematocrit or platelet cell volume <25 volume %, or oral anticoagulant therapy with an international normalized ratio >1.7.
17. Pregnancy, lactation, or parturition within the previous 30 days
18. Known serious sensitivity to radiographic contrast agents
19. Other serious, advanced, or terminal illness such that life expectancy is <1 year
20. Any other condition that the physician believes would pose a significant hazard to the patient if fibrinolytic therapy were initiated (e.g. amyloid angiopathy)
21. Uncompensated hypertension at study entry or hypertension requiring aggressive treatment to reduce blood pressure to nonhypertensive limits. Uncompensated hypertension is defined as systolic blood pressure >180 mmHg or diastolic blood pressure ≥105 mmHg on 3 repeated measures at least 10 minutes apart. Aggressive treatment is defined as the need for a continuous, parenteral antihypertensive, such as a nitroprusside drip, or the need to administer >3 doses of a parenteral antihypertensive, such as labetalol or Urapidil.
22. Evidence of ICH or SAH
23. DWI abnormality involving >1/3 of middle cerebral artery (MCA) territory
24. No perfusion deficit
25. Any intracranial pathology interfering with the assessment of diffusion and
perfusion abnormalities
26. Contraindications to MRI
Recruitment start date
01/06/2005
Recruitment end date
01/06/2007
Locations
Countries of recruitment
China
Trial participating centre
No.6
Beijing
100050
China
Sponsor information
Organisation
Ministry of Science and Technology of the People's Republic of China (China)
Sponsor details
15B
Fuxing Road
Beijing
100862
China
jenny760508@yahoo.com.cn
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
th Five-year National Key Technologies R&D Program (ref: 2004BA714B6)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list