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

Boehringer Ingelheim1,489 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,489

Conditions

Stroke

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Percentage of Participants With 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). It was measured at Day 90. Percentages are rounded to the nearest digits.

Time frame: At Day 90±7 days

Secondary Outcomes

Percentage of Participants With Major Neurological Improvement (National Institutes of Health Stroke Scale (NIHSS) Score of 0 or Improvement of at Least 4 Points Compared With Baseline

Total NIHSS score (0-42) = sum of 11 individual item scores, higher total scores meaning more severe deficits. indivudal domains: level of consciousness (LOC), best gaze, visual fields, facial paresis, motor function arms, motor function legs, limb ataxia, sensory, language, dysarthria, extinction and inattention. Mild strokes (NIHSS \< 6): High likelihood of good recovery and independence, Moderate strokes (NIHSS 6-15): Variable outcomes depending on timely intervention, Severe strokes (NIHSS \> 15): Lower likelihood of recovery without significant disability and higher risk of mortality. Percentages are rounded to the nearest digits.

Time frame: At 24 hours

Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-2

Percentage of participants with Modified Rankin Scale (mRS) score of 0-2 is presented. 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). It was measured at Day 90. Percentages are rounded to the nearest digits.

Time frame: At Day 90

Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Score

Total NIHSS score (0-42) = sum of 11 individual item scores, higher total scores meaning more severe deficits. indivudal domains: level of consciousness (LOC), best gaze, visual fields, facial paresis, motor function arms, motor function legs, limb ataxia, sensory, language, dysarthria, extinction and inattention. Restricted maximum likelihood (REML) based MMRM approach used to compare change from baseline in NIHSS score at day 90. If patient misses visit, missing data will not be imputed. The mixed effect model will handle missing data based on a likelihood method under MAR assumption. Change in NIHSS score from baseline = overall mean + treatment + visit + baseline NIHSS + age + time to drug administration since onset of stroke symptoms + treatment by visit interaction + baseline NIHSS by visit interaction + random error.

Time frame: At baseline and at Day 90

Distribution of Modified Rankin Scale (mRS)

Distribution of Modified Rankin Scale (mRS) is presented. 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). It was measured at Day 90.

Time frame: At Day 90

Percentage of Participants With 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. Percentages are rounded to the nearest digits.

Time frame: up to 90 days

Percentage of Participants With Symptomatic Intracerebral Haemorrhage (sICH) Per European Cooperative Acute Stroke Study (ECASS) Ⅲ Definition During On-treatment Period

Percentage of participants with Symptomatic Intracerebral Haemorrhage (sICH) per European Cooperative Acute Stroke Study (ECASS) Ⅲ definition during on-treatment period is presented. Percentages are rounded to the nearest digits.

Time frame: Up to 7 days.

Percentage of Participants Who Died by Day 90

Percentage of participants who died by day 90 is presented. Percentages are rounded to the nearest digits.

Time frame: up to 90 days

Percentage of Participants With Modified Rankin Scale (mRS) Score of 5 or 6

Percentage of participants with Modified Rankin Scale (mRS) score of 5 or 6 is presented. 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). It was measured at Day 90. Percentages are rounded to the nearest digits.

Time frame: At Day 90

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

Overview

Conditions

Interventions

Eligibility

Locations (55)

Outcomes

Primary Outcomes

Secondary Outcomes