A Study in Chinese Patients to Compare How Tenecteplase and Alteplase Given After a Stroke Improve Recovering of Physical Activity

Study Overview
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Brief Summary
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This study is open to Chinese adults who had an ischaemic stroke, which means that blood vessels in the brain are blocked. To resolve blood clots, people in the study get either tenecteplase or alteplase within 4 hours and 30 minutes after stroke. The purpose of this study is to compare how tenecteplase and alteplase improve peoples' recovering of physical activity. Alteplase is standard of care. Tenecteplase is a modified variant of alteplase that is easier to administer and is approved to treat heart attack. This study is to find out whether tenecteplase is as good as alteplase in people with ischaemic stroke. Participants are equally put into 2 treatment groups by chance. Participants in one group get tenecteplase as a single injection into a vein. Participants in the other group get alteplase as an injection into a vein (10% of the dose) and the remainder as an infusion over 1 hour. Participants are in the study for about 3 months. They are in the hospital for the first week after treatment. Then they visit the study site 1 and 3 months after treatment. At these visits, peoples' ability to independently carry out daily activities is assessed. Scores for physical activity are compared between both treatment groups. The doctors also regularly check the general health of the participants.

Official Title
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A Phase III Multi-centre, Prospective, Randomised, Open Label, Blinded Endpoint (PROBE), Active-controlled Parallel Group Trial to Assess Efficacy and Safety of Tenecteplase Versus Alteplase in Chinese Patients With Acute Ischaemic Stroke Within 4.5 Hours After Stroke Onset

Conditions
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Stroke

Intervention / Treatment
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* Drug: tenecteplase
* Drug: alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Diagnosis of ischaemic stroke with a measurable neurological deficit on National Institutes of Health Stroke Scale (NIHSS) (0< NIHSS ≤25); if NIHSS <4, patients have to be with at least a measurable deficit on motor power (upper or lower limbs ≥1) Stroke symptoms should have been present for at least 30 minutes (min) without significant improvement prior to randomisation Thrombolytic therapy can be initiated within 4.5 Hour(s) (h) of Acute ischaemic stroke (AIS) onset Patients with premorbid modified Rankin Scale (mRS) 0 or 1 Signed and dated written informed consent in accordance with good clinical practice (GCP) and local legislation prior to trial admission Exclusion Criteria: Evidence of intracranial haemorrhage on the Computed tomography (CT) scan or symptoms suggestive of subarachnoid haemorrhage, even if the CT scan is normal Patients who must or are expected to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial Acute bleeding diathesis, including but not limited to Known genetic predisposition to bleeding or significant bleeding disorder at present or within the past 6 Month(s) (m) Administration of heparin within the previous 48 h and activated partial thromboplastin time (aPTT) exceeding the upper limit of normal for laboratory measurement Current use of vitamin K based oral anticoagulants (e.g. warfarin) and a prolonged prothrombin time (International normalised Ratio (INR) > 1.7 or Prothrombin time (PT)>15 seconds (s)) or current use of novel oral anticoagulants (i.e. dabigitran, rivaroxiban, or apixiban) with prolongation of activated partial thromboplastin time (aPTT) and/or PT above the upper limit of the local laboratory reference range Platelet count of below 100,000/mm3 at screening Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) Recent traumatic external heart massage, obstetrical delivery, or recent puncture of a non-compressive blood-vessel (e.g. subclavian or jugular vein puncture) , within the past 10 days Known history of suspected intracranial haemorrhage or suspected subarachnoid haemorrhage from aneurysm Neoplasm with increased haemorrhagic risk Documented ulcerative gastrointestinal disease during the last 3 m, oesophageal varices, arterial aneurysm, or arterial/venous malformations Any known disorder associated with a significant increased risk of bleeding Bacterial endocarditis or pericarditis at screening Acute pancreatitis at screening Significant trauma or major surgery (according to the investigator's assessment) in the past 3 m Imaging demonstrates multi-lobar infarction (hypodensity >1/3 cerebral hemisphere) Severe uncontrolled arterial hypertension, e.g. systolic blood pressure (BP) >185 mmHg or diastolic BP >110 mmHg Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tenecteplase<br>Treatment Group | Drug: tenecteplase<br>* tenecteplase<br>|
| Active Comparator: alteplase<br>Active control group | Drug: alteplase<br>* alteplase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) score of 0 or 1 | Modified Rankin Scale (mRS) is a standardized measure that describes the extent of disability after a stroke. The mRS is a single item scale. It increases from 0 (no symptoms at all) to 6 (death). | up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major neurological improvement (National Institutes of Health Stroke Scale (NIHSS) score of 0 or improvement of at least 4 points compared with baseline) | National Institutes of Health Stroke Scale (NIHSS) is a 11-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 6 grades with 0 as normal, and there is an allowance for untestable items. | up to 24 hours | 
| Modified Rankin Scale (mRS) score of 0-2 |  | up to 90 days | 
| Change from baseline of National Institutes of Health Stroke Scale (NIHSS) score |  | up to 90 days | 
| Distribution of Modified Rankin Scale (mRS) |  | up to 90 days | 
| Barthel Index score ≥95 | The Barthel Index is an ordinal scale used to measure performance in activities of daily living (ADL). The Barthel Index consists of 10 items. The total score of the Barthel Index ranges from 0 to 100, and higher scores indicate better outcome. | up to 90 days | 
| Symptomatic Intracerebral Haemorrhage (sICH) per European Cooperative Acute Stroke Study (ECASS) Ⅲ definition during on-treatment period |  | up to 36 hours | 
| 90-day mortality |  | up to 90 days | 
| Modified Rankin Scale (mRS) score of 5 or 6 |  | up to 90 days |