Imaging-based Thrombolysis trial in Acute Ischemic Stroke -III

ISRCTN	ISRCTN03887874
DOI	https://doi.org/10.1186/ISRCTN03887874
Protocol serial number	5
Sponsor	Beijing Tiantan Hospital (China)
Funder	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

Submission date: 14/10/2007
Registration date: 30/10/2007
Last edited: 30/10/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Yongjun Wang
Scientific

Neurology Department
Beijing Tiantan Hospital
Tiantan Xili 6
Chongwen District
Beijing
100050
China

Email	yongjunwang111@yahoo.com.cn

Study information

Primary study design	Interventional
Study design	A prospective, multi-center, assessor-blind controlled trial
Secondary study design	Non randomised controlled trial
Scientific title
Study acronym	ITAIS- III
Study objectives	Whether the patients without occlusion or significant stenosis of the large vessels should receive thrombolysis had been focused on and questioned for a long time. However, there is still no large Randomised Controlled Trial (RCT) to prove if these patients can benefit from thrombolysis. The objective of this trail is to investigate: 1. For the selected acute ischemic stroke patients without large vessels occlusion or significant stenosis, whether the IntraVenous (IV) thrombolysis can improve the clinical outcome if the mismatch exists on CTP/Computed Tomography Angiography-Source Images (CTA-SI) scan in 3-9 hr time-window 2. For the selected acute ischemic stroke patients without large vessels occlusion or significant stenosis, whether the IV thrombolysis can improve the blood perfusion of brain if the mismatch exists on CT perfusion (CTP)/CTA-SI scan in 3-9 hr time-window 3. For the selected acute ischemic stroke patients without large vessels occlusion or significant stenosis, but the mismatch exists on CTP/CTA-SI scan in 3-9 hr time-window, whether the safety of IV thrombolysis is better than the NINDS trial which was in 3 hr window or implemented on the patients with large vessels occlusion or significant stenosis in 3-9 hr time-window.
Ethics approval(s)	Approval gained from the Beijing Tiantan Hospital Capital Medical University Ethics Board on October 10, 2006.
Health condition(s) or problem(s) studied	Acute ischemic stroke
Intervention	Patients included were divided into recombinant tissue Plasminogen Activator (rt-PA) (0.9 mg/kg) intravenous thrombolysis group and regular treatment group according to the intention of doctors and patients.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Recombinant tissue Plasminogen Activator (rt-PA)
Primary outcome measure(s)	Proportion of participants who achieve the following: 1. Reperfusion improvement, 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 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
Key secondary outcome measure(s)	Proportion of participants who achieve the following: 1. mRS 0 to 2 at 90 days 2. Barthel Index (BI) score 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
Completion date	01/06/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	200
Key inclusion criteria	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 Institutes of Health Stroke Scale (NIHSS) score greater than 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
Key exclusion criteria	1. Evidence of IntraCranial Haemorrhage (ICH), brain tumors, vascular malformation, aneurysm, SubArachnoid Hemorrhage (SAH) 2. Major infarct involving greater than 1/3 of Middle Cerebral Artery (MCA) territory on the CTA-SI 3. Presenting obvious neurologic deficits because of past stroke (mRS >2) 4. Severe stroke as assessed clinically (e.g. The National Institute of Health Stroke Scale [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
Date of first enrolment	01/10/2007
Date of final enrolment	01/06/2010

Locations

Countries of recruitment

China

Study participating centre

Neurology Department

Beijing
100050
China

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan