UMIN-CTR Clinical Trial

Public title

Extending the time for Thrombolysis in Emergency Neurological Deficits (International)

Acronym

EXTEND (International)

Scientific Title

Extending the time for Thrombolysis in Emergency Neurological Deficits (International)

Scientific Title:Acronym

EXTEND (International)

Region

Japan	Asia(except Japan)	Australia

Condition

Acute ischemic stroke

Classification by specialty

Neurology	Radiology	Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To test the hypothesis that ischaemic stroke patients of similar age and stroke severity selected with significant perfusion-diffusion mismatch at 3-9 hours post onset of stroke (based on local legally accepted practice and guideline) will have improved clinical outcomes when given intravenous tPA compared to placebo.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase III

Primary outcomes

Modified Rankin Scale (mRS) 0-1 at 3 months

Key secondary outcomes

Categorical shift in mRS at 3 months.
Change in >= 8 NIHSS points or reaching <= 1 NIHSS points on this scale.
Death due to any cause.
Symptomatic ICH.
Reperfusion at 24 hrs post stroke.
Recanalisation at 24 hrs post stroke.
Infarct growth on DWI within 24 hrs.
Recurrent stroke at 3 months.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

Institution consideration

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

tPA: Tissue Plasminogen Activator (tPA) is given intravenously at the dose of 0.6mg/kg up to a maximum of 60mg, 10% as bolus and the remainder over 1 hour.

Interventions/Control_2

Placebo: Placebo is given intravenously, 10% as bolus and the remainder over 1 hour.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Patients presenting with acute ischemic stroke.
2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.
3. Treatment onset can commence after 3 hours and up to and including 9 hours after stroke onset according to registered product information.
4. Patients who wake with stroke may be included if neurological and other exclusion criteria are satisfied. These wake up strokes are defined as having no symptoms at sleep onset, but stroke symptoms on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking. The maximum time window for randomisation is then 9 hours from the mid-point as described.
5. NIHSS score of 4 - 26 with clinical signs of hemispheric infarction.
Imaging inclusion criteria.
6. Perfusion-diffusion mismatch: Using a Tmax > 6 second delay, a perfusion volume (PWI) to DWI volume (DWI) ratio of greater than 1.2, and a PWI-DWI difference of greater than 10 ml.
7. A DWI lesion of less than or equal to 70 ml.

Key exclusion criteria

1. Intracranial haemorrhage identified by CT or MRI.
2. Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of < 4 at randomization.
3. Pre-stroke mRS score of >= 2.
4. Contra indication to imaging with MR with contrast agents.
5. Infarct core >1/3 MCA territory.
6. Participation in any investigational study in the previous 30 days.
7. Any terminal illness such that patient would not be expected to survive more than 1 year.
8. Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
9. Pregnant women.
10. Previous stroke within last three months.
11. Recent past history or clinical presentation of ICH, subarachnoid haemorrhage, arterio-venous malformation, aneurysm, or cerebral neoplasm.
12. Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6).
13. Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
14. Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) prior to study entry is permitted.
15. Clinically significant hypoglycaemia.
16. Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits.
17. Hereditary or acquired haemorrhagic diathesis.
18. Gastrointestinal or urinary bleeding within the preceding 21 days.
19. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
20. Exposure to a thrombolytic agent within the previous 72 hours.

Target sample size

400

Name of lead principal investigator

1st name
Middle name
Last name	Professor Geoffrey Donnan

Organization

National Stroke Research Institute

Division name

Director

Zip code

Address

245 Burgundy Street, Heidelberg, VIC 3084, Australia.

TEL

61-3-9496-2699

Email

Name of contact person

1st name
Middle name
Last name	Kazunori Toyoda, MD, PhD

Organization

National Cerebral and Cardiovascular Center

Division name

Department of Cerebrovascular Medicine

Zip code

Address

5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.

TEL

06-6833-5012

Homepage URL

Email

toyoda@hsp.ncvc.go.jp

Institute

National Stroke Research Institute (NSRI)Melbourne Brain Centre

Institute

Department

Personal name

Organization

Japan Cardiovascular Research Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Australia

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT00887328

Org. issuing International ID_1

Clinical trials. gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立循環器病センター 脳血管内科・脳神経内科（大阪府）
中村記念病院 脳神経外科（北海道）
聖マリアンナ医科大学 神経内科（神奈川県）　　　　　　
熊本大学大学院　生命科学研究部・神経内科（熊本県）

Date of disclosure of the study information

2011

Year

10

Month

24

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2011

Year

06

Month

27

Day

Date of IRB

Anticipated trial start date

2012

Year

01

Month

01

Day

Last follow-up date

2014

Year

09

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

In April 2012, the principal investigator concluded that we were not able to participate the EXTEND trial because of a low dose (0.6mg/kg) use of tPA in Japan.
Consequently, we abandoned to start the trial.

Registered date

2011

Year

10

Month

21

Day

Last modified on

2013

Year

04

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007798