Contact information
Type
Scientific
Primary contact
Prof Yongjun Wang
ORCID ID
Contact details
Neurology Department
Beijing Tiantan Hospital
Tiantan Xili 6
Chongwen District
Beijing
100050
China
yongjunwang111@yahoo.com.cn
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
6
Study information
Scientific title
Acronym
ITAIS-II
Study hypothesis
To extend the time window for thrombolysis with recombinant tissue Plasminogen Activator (rtPA) in acute ischemic stroke patients, the most significant imaging for selecting patients to implement rt-PA thrombolysis is multi-Computerised Tomography (CT) which includes Non-Enhanced CT (NECT), Computed Tomography Angiography (CTA) and CT Perfusion (CTP), or multi-MR which includes Magnetic Resonance Angiography (MRA), Diffusion-Weighted Imaging (DWI) and Perfusion-Weighted Imaging (PWI). But CT is not only more universal but also cheaper and time-saving than MR. The objective of this trail is to investigate:
1. For the selected acute ischemic stroke patients with CTP/CTA-Source Images (CTA-SI) mismatch in 3-9 hr time-window, whether the efficacy and safety of IntraVenous (IV) thrombolysis are equivalent with the routine and the classical National Institute of Neurological Disorders and Stroke (NINDS) trial which were in 3 hr time-window
2. Whether m-CT in super-early stage of stroke can predict the outcome of the patient and the efficacy of thrombolysis
3. Whether the improvement of m-CT imaging can be a substitutive indication to evaluate the outcome, and whether there is a significant correlation between the improvement and the clinical outcome
Ethics approval
Approval gained from the Beijing Tiantan Hospital Capital Medical University Ethics Board on October 10, 2006.
Study design
A prospective, multi-center, assessor-blind controlled study.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Acute ischemic stroke
Intervention
In all trial centers, consecutive acute ischemic stroke patients within 9 hr time-window will be screened, and those within 3-9 hr time-window must undergo mCT examination. All patients who meet the inclusion criteria will be included in this trial and will be treated by rt-PA 0.9 mg/kg (IV) thrombolysis. 10% of the total dose will be given as a bolus in 1 minute, and the remaining will be given as an infusion over 1 hr. All participants will be divided into 3hr time-window group and 3-9 hr time-window group.
Intervention type
Drug
Phase
Not Specified
Drug names
Recombinant tissue Plasminogen Activator (rtPA)
Primary outcome measure
1. Reperfusion improvement was assessed 24 to 48 hours post-treatment and defined as either greater than or equal to 30% reduction of Mean Transit Time (MTT) volume of abnormality or greater than or equal to 2 points improvement on the TICI grading scheme
2. Good clinical outcome at 90 days defined as a modified Rankin Score (mRS) of 0-1
3. Intracerebral haemorrhage within 24-36 h after thrombolysis
Secondary outcome measures
Proportion of participants who achieve the following:
1. mRS 0 to 2 at 90 days
2. Barthel Index (BI) score of 75 to 100 at 90 days
3. NIHSS 4 points improvement or 0-1 at 2 hours after treatment
4. NIHSS 4 points improvement or 0-1 at 24 to 48 hours
5. NIHSS 4 points improvement or 0-1 at day 7
Overall trial start date
01/10/2007
Overall trial end date
01/06/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
For patients within 3 hrs time-windows, the only inclusion criterion for rt-PA (IV) thrombolysis is to satisfy the product instruction of rt-PA. The following are the inclusion criteria for patients within 3-9 hrs time-windows:
1. Female or male inpatients
2. Age 18-80 years
3. Clinical diagnosis of ischaemic stroke
4. Onset of symptoms within 3-9 hours prior to initiation of thrombolysis treatment
5. Stroke symptoms present for at least 30 minutes and has not significantly improved before treatment
6. The National Institute of Health Stroke Scale (NIHSS) score of greater or equal to 4
7. m-CT screening to be started within 8.5 hrs after stroke onset
8. Perfusion abnormality of CT scan >2cm in diameter involving hemisphere
9. CT perfusion/CTA source image mismatch greater than or equal to 20%
10. CTA shows occlusion or significant stenosis of large vessels (Thrombolysis in Cerebral Ischemia [TICI] grade is 0 or 1)
11. Patients are willing to receive thrombolysis treatment and to give informed consent
12. Patients are willing and able to comply with the study protocol
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
200
Participant exclusion criteria
For patients within 3 hrs time-windows, the only exclusion criterion for rt-PA (IV) thrombolysis is to satisfy the product instruction of rt-PA. The following are the exclusion criteria for patients within 3-9 hrs time-windows:
1. Evidence of IntraCranial Haemorrhage (ICH), brain tumors, vascular malformation, aneurysm, SubArachnoid Hemorrhage (SAH)
2. Major infarct involving >1/3 of MCA territory on the CTA-SI
3. Presenting obvious neurologic deficits because of past stroke (modified Rankin Scale [mRS] >2)
4. Severe stroke as assessed clinically (e.g. NIHSS >25) and/or by appropriate, magnetic imaging techniques
5. Seizure at onset of stroke
6. Prior stroke within the last 3 months
7. Patients with any history of prior stroke and concomitant diabetes
8. Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
9. Platelet count of below 100,000/mm3.
10. 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 >185 mm Hg or diastolic blood pressure >=110 mm Hg on 3 repeated measures at least 10 minutes apart
11. Blood glucose <50 or >400 mg/dl
12. Known haemorrhagic diathesis within the last 6 months
13. Patients receiving oral anticoagulants, e.g. warfarin sodium, and coagulant response time (INR) >1.5
14. Known history of or suspected intracranial haemorrhage including subarachnoid haemorrhage
15. Pregnancy or lactation
16. Any history of severe central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
17. Haemorrhagic retinopathy,e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy)
18. Bacterial endocarditis, pericarditis
19. Prolonged traumatic external heart massage, or recent (less than 10 days) obstetrical delivery or recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture)
20. Acute pancreatitis
21. Documented ulcerative gastrointestinal disease during the last 3 months
22. Oesophageal varices, arterial aneurysm, arterial/venous malformation
23. Neoplasm with increased bleeding risk
24. Severe liver disease, including hepatic failure, cirrhosis, portal hypertension, oesophageal varices and active hepatitis
25. Major surgery or significant trauma in past 10 days
26. Known serious sensitivity to alteplase
Recruitment start date
01/10/2007
Recruitment end date
01/06/2010
Locations
Countries of recruitment
China
Trial participating centre
Neurology Department
Beijing
100050
China
Sponsor information
Organisation
Beijing Tiantan Hospital (China)
Sponsor details
Beijing Tiantan Hospital
Tiantan Xili 6
Chongwen District
Beijing
100050
China
yongjunwang111@yahoo.com.cn
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
The Ministry of Science and Technology and the Ministry of Health of the People's Republic of China - the key scientific research program of the 11th National Five-Year Planning of China
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
1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19236499
Publication citations
-
Results
Wang Y, Liao X, Zhao X, Wang C, Liu L, Zhou Y, Wang C, Xue J, Gao P, Dong K, Ji X, Wang Y, , Imaging-based thrombolysis trial in acute ischemic stroke-II (ITAIS-II)., Int J Stroke, 2009, 4, 1, 49-53; discussion 49, doi: 10.1111/j.1747-4949.2009.00245.x.