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

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Stroke

Treatments: Drug: alteplase; Drug: tenecteplase

Study type: Interventional

Funder types: Industry

Identifiers

NCT04915729

1123-0040

Details and patient eligibility

About

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.

Enrollment: 1,489 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,489 participants in 2 patient groups

Tenecteplase treatment group

Experimental group

Description:

Chinese patients with AIS were screened (visit 1) and randomised (visit 2a) when admitted. Patients received a single dose of tenecteplase, 0.25 mg/kg via intravenous (iv) bolus no later than 4.5 hours (h) after symptom onset. Visits on Day 1 consisted of two further visits (Visit 2b and Visit 2c) that were performed 1 h and 2 h after the start of the treatment. Visits 3 to 5 for continuous follow-up were performed on day 2, 8 and 30 after the start of the treatment. Treated patient performed a 90-day follow-up visit after the treatment to complete the study.

Treatment:

Drug: tenecteplase

Alteplase active control group

Active Comparator group

Description:

Chinese patients with AIS were screened (visit 1) and randomised (visit 2a) when admitted. Patients received a single dose of alteplase, 0.9 mg/kg, 10% via intravenous (iv) bolus and the remaining 90% of the total dose administered as an iv infusion over 1 h no later than 4.5 hours (h) after symptom onset. Visits on Day 1 consisted of two further visits (Visit 2b and Visit 2c) that were performed 1 h and 2 h after the start of the treatment. Visits 3 to 5 for continuous follow-up were performed on day 2, 8 and 30 after the start of the treatment. Treated patient performed a 90-day follow-up visit after the treatment to complete the study.

Treatment:

Drug: alteplase