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

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

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 Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: tenecteplase; Drug: alteplase

• Study Type: Interventional
• Enrollment (Actual): 1490
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• China
  • Baotou, China, 14000
    • Inner Mongolia Baogang Hospital
  • Beijing, China, 100020
    • Beijing Chao-Yang Hospital
  • Beijing, China, 100730
    • Beijing Tongren Hospital
  • Beijing, China, 100044
    • Beijing Tsinghua Changgung Hospital
  • Beijing, China, 100070
    • Beijing Tiantan Hospital affiliated to Cap Med University
  • Changchun, China, 130031
    • The First Hospital of Jilin University
  • Changsha, China, 410013
    • The Third Xiangya Hospital of Central South University
  • Chifeng, China, 025350
    • Hexigten Banner Mongolian Traditional Chinese medicine hospital
  • Chongqing, China, 400016
    • Second Affiliated Hospital Chongqing Medical University
  • Dalian, China, 116021
    • Center Hospital of Dalian
  • Daqing, China, 163000
    • Daqing People's Hospital
  • Dongying, China, 257091
    • Shengli Oilfield Central Hospital
  • Guangzhou, China, 510150
    • Third Affiliated Hospital of Guangzhou Medical University
  • Guiyang, China, 550004
    • The Affiliated Hospital Of Guizhou Medical University
  • Hangzhou, China, 310014
    • Zhejiang Province People's Hospital
  • Hangzhou, China, 310015
    • The Affiliated Hospital of Hangzhou Normal University
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital Zhejiang University School of Medicine
  • Hangzhou, China, 210011
    • The Second Affiliated Hospital of Nanjing Medical University
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
  • Huai'an, China, 223002
    • Huai'an Second People's Hospital
  • Inner Mongolia, China, 014010
    • The first affiliated hospital of Baotou medical college
  • Jiaxing, China, 314001
    • The second Hospital of Jiaxing
  • Jinan, China, 250013
    • Center Hospital of Jinan
  • Jinhua, China, 321000
    • Jinhua Municipal Central Hospital
  • Lianyungang, China, 222002
    • The First People's Hospital of Lianyungang
  • Linfen, China, 041000
    • Linfen Central Hospital
  • Linhai, China, 317000
    • Taizhou Hospital of Zhejiang Province
  • Linyi, China, 276000
    • Linyi People's Hospital
  • Linyi, China, 276000
    • The First People's Hospital of Tancheng County
  • Nanchang, China, 330006
    • The First Affiliated Hospital Of NanChang University
  • Nanjing, China, 210009
    • Zhongda Hospital Southeast University
  • Nanning, China, 530000
    • The First People's Hospital of Nanning
  • Nantong, China, 226001
    • The First People's Hospital of Nantong
  • Ruian, China, 325200
    • Ruian People's Hospital
  • Shanghai, China, 200065
    • Tongji Hospital, Tongji University
  • Shanghai, China, 200051
    • Tongren hospital, Shanghai Jiaotong University School of Medicine
  • Shanghai, China, 200120
    • Shanghai East Hospital
  • Shanghai, China, 200137
    • Shanghai Seventh People's Hospital
  • Shenyang, China, 110000
    • Affiliated Central Hospital of Shenyang Medical College
  • Shenyang, China, 110000
    • The First People's Hospital of Shenyang
  • Shenzhen, China, 518000
    • Peking University Shenzhen Hospital
  • Shijiazhuang, China, 050000
    • The Second Hospital of Hebei Medical University
  • Suzhou City, China, 215004
    • The Second Affiliated Hospital of Soochow University
  • Tianjin, China, 300000
    • The 2nd Hospital of Tianjin Medical University
  • Tianjin, China, 30052
    • Tianjin Medical University General Hospital
  • Tianjin, China, 300192
    • The First Center Hospital of Tianjin
  • Wuhan, China, 430022
    • Wuhan Union Hospital
  • Wuxi, China, 214043
    • WuXi People's Hospital
  • Xianyang, China, 712000
    • XianYang Hospital OF Yan'an University
  • Xinxiang, China, 453000
    • Xinxiang Central Hospital
  • Xuancheng, China, 242000
    • The People's Hospital Of Xuancheng City
  • Xuzhou, China, 221003
    • Affiliated Hospital, Xuzhou Medical college
  • Yangzhou, China, 225001
    • Affiliated Hospital of Yangzhou University
  • Yantai, China, 264010
    • Yantai Yuhuangding Hospital
  • Yiyang, China, 413000
    • Yiyang Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tenecteplase; Treatment Group	Drug: tenecteplase; tenecteplase
Active Comparator: alteplase; Active control group	Drug: alteplase; alteplase

What is the study measuring?

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
90-day mortality		up to 90 days
Modified Rankin Scale (mRS) score of 5 or 6		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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): October 8, 2023
• Study Completion (Actual): October 8, 2023

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: 1123-0040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No