Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND)
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ClinicalTrials.gov Identifier: NCT00887328 |
Recruitment Status :
Completed
First Posted : April 23, 2009
Last Update Posted : August 31, 2018
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Condition or disease | Intervention/treatment | Phase |
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Stroke | Drug: Tissue Plasminogen Activator (Alteplase) Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 180 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Extending the Time for Thrombolysis in Emergency Neurological Deficits |
Study Start Date : | June 2010 |
Actual Primary Completion Date : | August 27, 2018 |
Actual Study Completion Date : | August 27, 2018 |

Arm | Intervention/treatment |
---|---|
Experimental: IV tPA
intravenous tissue plasminogen activator
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Drug: Tissue Plasminogen Activator (Alteplase)
0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour
Other Names:
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Placebo Comparator: Placebo |
Drug: Placebo
placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug |
- Modified Rankin Scale (mRS) 0-1 [ Time Frame: 3 months ]
- Categorical shift in modified Rankin Score (mRS) [ Time Frame: 3 months ]
- Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale [ Time Frame: 3 months ]
- Death due to any cause [ Time Frame: 3 months ]
- Symptomatic ICH [ Time Frame: 24 hours ]Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS
- Reperfusion [ Time Frame: 24 hours ]
- Recanalisation [ Time Frame: 24 hours ]
- Infarct growth [ Time Frame: 24 hours ]Difference in volumetric DWI volume between baseline and 24 hour MRI
- Recurrent stroke [ Time Frame: 3 and 12 months ]
- Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) [ Time Frame: 3 and 12 months ]
- Quality of life (Stroke Impact Scale) [ Time Frame: 3 and 12 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients presenting with hemispheric acute ischaemic stroke
- Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
- Patient's age is ≥18 years
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Treatment onset can commence within ≥ 3 - 9 hours after stroke onset according to registered product information, or within 4.5 - 9 hours according to locally accepted guidelines*.
(*Guidelines are currently under international review - advisory statement issued by the Stroke Council, American Heart Association and American Stroke Association)
- 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.
- NIHSS score of ≥ 4 - 26 with clinical signs of hemispheric infarction.
- Penumbral mismatch - A "hypo-perfusion to core" volume ratio of greater than 1.2 and an absolute difference greater than 10mL (using a MR or CT Tmax > 6 second delay) between perfusion lesion and MR-DWI or CT-CBF core lesion.
- An ischaemic core lesion volume of less than or equal to 70 ml using MR-DWI or CT-CBF ** Patients may be consented before or after penumbral screening depending upon local practice. The entire cohort of patients consented onto the study will be followed up with clinical assessments and biomarker studies regardless of eligibility for randomisation to treatment based on penumbral mismatch criteria
Exclusion Criteria:
- Intracranial haemorrhage (ICH) identified by CT or MRI
- 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
- Pre-stroke MRS score of ≥ 2 (indicating previous disability)
- Contra indication to imaging with MR with contrast agents
- Infarct core >1/3 MCA territory qualitatively
- Participation in any investigational study in the previous 30 days
- Any terminal illness such that patient would not be expected to survive more than 1 year
- Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as haemolytic uremic syndrome or thrombotic thrombocytopenic purpura). The judgment is left to the discretion of the Investigator.
- Pregnant women (clinically evident)
- Previous stroke within last three months
- Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
- Current use of oral anticoagulants or a prolonged prothrombin time (INR > 1.7) if the patient is on warfarin
- Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and an activated prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
- 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.
- Clinically significant hypoglycaemia.
- 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. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator.
- Hereditary or acquired haemorrhagic diathesis
- Gastrointestinal or urinary bleeding within the preceding 21 days
- Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
- Exposure to a thrombolytic agent within the previous 72 hours
- Clinically deemed eligible for Endovascular Clot Retrieval (ECR) treatment by the treating team

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00887328

Principal Investigator: | Geoffrey Donnan, MD FRACP | The Florey Institute of Neuroscence and Mental Health | |
Principal Investigator: | Stephen Davis, MD FRACP | University of Melbourne |
Responsible Party: | Neuroscience Trials Australia |
ClinicalTrials.gov Identifier: | NCT00887328 |
Other Study ID Numbers: |
NTA0901 |
First Posted: | April 23, 2009 Key Record Dates |
Last Update Posted: | August 31, 2018 |
Last Verified: | August 2018 |
ischemic stroke ischemic penumbra magnetic resonance imaging MRI diffusion imaging DWI |
perfusion imaging PWI thrombolysis alteplase tPA EPITHET |
Emergencies Disease Attributes Pathologic Processes Tissue Plasminogen Activator |
Plasminogen Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |