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StrokePhase 3ORIGINALNCT04915729

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

A Phase 3 study testing tenecteplase and alteplase in people with Stroke, run by Boehringer Ingelheim at 55 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke
What is being tested?
tenecteplase and alteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,489 participants
Where
55 sitesChina
Study dates
22 Jun 2021to 8 Oct 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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 locations and contacts

55 sites in 1 country.

55 sites in 1 country

China55 sites

  • Inner Mongolia Baogang Hospital

    Baotou, 14000

  • Beijing Chao-Yang Hospital

    Beijing, 100020

  • Beijing Tsinghua Changgung Hospital

    Beijing, 100044

  • Beijing Tiantan Hospital affiliated to Cap Med University

    Beijing, 100070

  • Beijing Tongren Hospital

    Beijing, 100730

  • The First Hospital of Jilin University

    Changchun, 130031

  • The third xiangya hospital of Central South University

    Changsha, 410013

  • Hexigten Banner Mongolian Traditional Chinese medicine hospital

    Chifeng, 025350

  • Second Affiliated Hospital Chongqing Medical University

    Chongqing, 400016

  • Center Hospital of Dalian

    Dalian, 116021

  • Daqing People's Hospital

    Daqing, 163000

  • Shengli Oilfield central hospital

    Dongying, 257091

  • Third Affiliated Hospital of Guangzhou Medical University

    Guangzhou, 510150

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, 550004

  • The Second Affiliated Hospital Zhejiang University School of Medicine

    Hangzhou, 310009

  • Zhejiang Province People's Hospital

    Hangzhou, 310014

  • The Affiliated Hospital of Hangzhou Normal University

    Hangzhou, 310015

  • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

    Hangzhou, 310016

  • Huai'an Second People's Hospital

    Huai'an, 223002

  • The First Affiliated Hospital of Baotou Medical College

    Inner Mongolia, 014010

  • The second Hospital of Jiaxing

    Jiaxing, 314001

  • Center Hospital of Jinan

    Jinan, 250013

  • Jinhua Municipal Central Hospital

    Jinhua, 321000

  • The first People's Hospital of Lianyungang

    Lianyungang, 222002

  • Linfen Central Hospital

    Linfen, 041000

  • Linyi People's Hospital

    Linyi, 276000

  • The First People's Hospital of Tancheng County

    Linyi, 276000

  • The First Affiliated Hospital of Nanchang University

    Nanchang, 330006

  • Zhongda Hospital Southeast University

    Nanjing, 210009

  • The Second Affiliated Hospital of Nanjing Medical University

    Nanjing, 210011

  • The First People's Hospital of Nanning

    Nanning, 530000

  • The First People's Hospital of Nantong

    Nantong, 226001

  • Ruian People's Hospital

    Ruian, 325200

  • Tongren hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, 200051

  • Tongji Hospital, Tongji University

    Shanghai, 200065

  • Shanghai East Hospital

    Shanghai, 200120

  • Shanghai Seventh People's Hospital

    Shanghai, 200137

  • Affiliated Central Hospital of Shenyang Medical College

    Shenyang, 110000

  • The First People's Hospital of Shenyang

    Shenyang, 110000

  • Peking University Shenzhen Hospital

    Shenzhen, 518000

  • The Second Hospital of Hebei Medical University

    Shijiazhuang, 050000

  • The Second Affiliated Hospital of Soochow University

    Suzhou, 215004

  • Taizhou Hospital of Zhejiang Province

    Taizhou, 317099

  • The 2nd Hospital of Tianjin Medical University

    Tianjin, 300000

  • The First Center Hospital of Tianjin

    Tianjin, 300192

  • Tianjin Medical University General Hospital

    Tianjin, 30052

  • Wuhan Union Hospital

    Wuhan, 430022

  • Wuxi People's Hospital

    Wuxi, 214043

  • Xianyang Hospital of Yan'an University

    Xianyang, 712000

  • Xinxiang Central Hospital

    Xinxiang, 453000

  • The People's Hospital Of Xuancheng City

    Xuancheng, 242000

  • Affiliated Hospital, Xuzhou Medical college

    Xuzhou, 221006

  • Affiliated Hospital of Yangzhou University

    Yangzhou, 225001

  • Yantai Yuhuangding Hospital

    Yantai, 264010

  • Yiyang Central Hospital

    Yiyang, 413000

Other trials in China

About this study

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

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.

Conditions
Stroke
Being tested
tenecteplase, alteplase
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tenecteplaseDrug

    tenecteplase

  • alteplaseDrug

    alteplase

Study groups in NCT04915729
Study groupRoleWhat they receive
Tenecteplase treatment groupExperimentalChinese 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.
Receives: Drug: tenecteplase
Alteplase active control groupActive comparatorChinese 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.
Receives: Drug: alteplase

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At Day 90±7 days

Secondary outcomes (8)

  1. 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.

    Measured: At 24 hours

  2. 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.

    Measured: At Day 90

  3. 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.

    Measured: At baseline and at Day 90

  4. 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.

    Measured: At Day 90

  5. 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.

    Measured: up to 90 days

  6. 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.

    Measured: Up to 7 days.

  7. 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.

    Measured: up to 90 days

  8. 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.

    Measured: At Day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start22 Jun 2021
  3. Primary completion8 Oct 2023
  4. Study completion8 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,489 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04915729
Sponsor's protocol ID
1123-0040
Acronym
ORIGINAL
Status last verified
Dec 2024
First submitted
4 Jun 2021
Last updated
10 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Meng X, Li S, Dai H, Lu G, Wang W, Che F, Geng Y, Sun M, Li X, Wang Y. Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study. Stroke Vasc Interv Neurol. 2024 May 7;4(4):e001363. doi: 10.1161/SVIN.124.001363. eCollection 2024 Jul.

    PubMed 41585404

  • Meng X, Li S, Dai H, Lu G, Wang W, Che F, Geng Y, Sun M, Li X, Li H, Wang Y. Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial. JAMA. 2024 Nov 5;332(17):1437-1445. doi: 10.1001/jama.2024.14721.

    PubMed 39264623

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tenecteplase and alteplase in people with Stroke, run by Boehringer Ingelheim at 55 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Modified Rankin Scale (mRS) Score of 0 or 1 (time frame: At Day 90±7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04915729, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.

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ORIGINAL Clinical Trial NCT04915729 | AzTrials