Clinical trial NCT04915729: A Study in Chinese Patients to Compare How Tenecteplase and Alteplase Given After a Stroke Improve Recovering of Physical Activity
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-06-07
Enrollment: 1489
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Modified Rankin Scale (mRS) Score of 0 or 1
timeFrame: At Day 90±7 days
Secondary outcomes:
measure: 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
timeFrame: At 24 hours
measure: Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-2
timeFrame: At Day 90
measure: Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Score
timeFrame: At baseline and at Day 90
measure: Distribution of Modified Rankin Scale (mRS)
timeFrame: At Day 90
measure: Percentage of Participants With Barthel Index Score ≥95
timeFrame: up to 90 days
measure: Percentage of Participants With Symptomatic Intracerebral Haemorrhage (sICH) Per European Cooperative Acute Stroke Study (ECASS) Ⅲ Definition During On-treatment Period
timeFrame: Up to 7 days.
measure: Percentage of Participants Who Died by Day 90
timeFrame: up to 90 days
measure: Percentage of Participants With Modified Rankin Scale (mRS) Score of 5 or 6
timeFrame: At Day 90
Other outcomes:
Locations:
city: Baotou
country: China
facility: Inner Mongolia Baogang Hospital
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: Beijing Tiantan Hospital affiliated to Cap Med University
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The third xiangya hospital of Central South University
city: Chifeng
country: China
facility: Hexigten Banner Mongolian Traditional Chinese medicine hospital
city: Chongqing
country: China
facility: Second Affiliated Hospital Chongqing Medical University
city: Dalian
country: China
facility: Center Hospital of Dalian
city: Daqing
country: China
facility: Daqing People's Hospital
city: Dongying
country: China
facility: Shengli Oilfield central hospital
city: Guangzhou
country: China
facility: Third Affiliated Hospital of Guangzhou Medical University
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Province People's Hospital
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
city: Inner Mongolia
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Jiaxing
country: China
facility: The second Hospital of Jiaxing
city: Jinan
country: China
facility: Center Hospital of Jinan
city: Jinhua
country: China
facility: Jinhua Municipal Central Hospital
city: Lianyungang
country: China
facility: The first People's Hospital of Lianyungang
city: Linfen
country: China
facility: Linfen Central Hospital
city: Linyi
country: China
facility: Linyi People's Hospital
city: Linyi
country: China
facility: The First People's Hospital of Tancheng County
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
city: Nanning
country: China
facility: The First People's Hospital of Nanning
city: Nantong
country: China
facility: The First People's Hospital of Nantong
city: Ruian
country: China
facility: Ruian People's Hospital
city: Shanghai
country: China
facility: Tongren hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Tongji Hospital, Tongji University
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Shanghai
country: China
facility: Shanghai Seventh People's Hospital
city: Shenyang
country: China
facility: Affiliated Central Hospital of Shenyang Medical College
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Suzhou City
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Tianjin
country: China
facility: The 2nd Hospital of Tianjin Medical University
city: Tianjin
country: China
facility: The First Center Hospital of Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Wuxi
country: China
facility: Wuxi People's Hospital
city: Xianyang
country: China
facility: Xianyang Hospital of Yan'an University
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
city: Xuancheng
country: China
facility: The People's Hospital Of Xuancheng City
city: Xuzhou
country: China
facility: Affiliated Hospital, Xuzhou Medical college
city: Yangzhou
country: China
facility: Affiliated Hospital of Yangzhou University
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Yiyang
country: China
facility: Yiyang Central Hospital
Study officials:
References: