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NCT04915729: ORIGINAL

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

Completed Phase 3 Results posted Last updated 10 December 2024
What this trial tests

Phase 3 trial testing tenecteplase in Stroke in 1,489 participants. Completed in 8 October 2023.

Timeline
22 June 2021
Primary endpoint
8 October 2023
8 October 2023

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposetreatment
Enrollment1,489
Start date22 June 2021
Primary completion8 October 2023
Estimated completion8 October 2023
Sites55 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Stroke. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Modified Rankin Scale (mRS) Score of 0 or 1 Primary · At Day 90±7 days

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.

GroupValue95% CI
Tenecteplase Treatment Group72.7
Alteplase Active Control Group70.3
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 Secondary · At 24 hours

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.

GroupValue95% CI
Tenecteplase Treatment Group48.0
Alteplase Active Control Group45.0
Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-2 Secondary · At Day 90

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.

GroupValue95% CI
Tenecteplase Treatment Group80.9
Alteplase Active Control Group79.9
Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Score Secondary · At baseline and at Day 90

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. Cha

GroupValue95% CI
Tenecteplase Treatment Group-3.47± 0.34
Alteplase Active Control Group-3.02± 0.34
Distribution of Modified Rankin Scale (mRS) Secondary · At Day 90

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.

mRS score = 0
GroupValue95% CI
Tenecteplase Treatment Group40.3
Alteplase Active Control Group40.5
mRS score = 1
GroupValue95% CI
Tenecteplase Treatment Group30.1
Alteplase Active Control Group28.2
mRS score = 2
GroupValue95% CI
Tenecteplase Treatment Group7.8
Alteplase Active Control Group9.4
mRS score = 3
GroupValue95% CI
Tenecteplase Treatment Group6.7
Alteplase Active Control Group5.5
mRS score = 4
GroupValue95% CI
Tenecteplase Treatment Group4.8
Alteplase Active Control Group6.4
mRS score = 5
GroupValue95% CI
Tenecteplase Treatment Group1.9
Alteplase Active Control Group1.6
mRS score = 6
GroupValue95% CI
Tenecteplase Treatment Group4.6
Alteplase Active Control Group6.0
missing
GroupValue95% CI
Tenecteplase Treatment Group3.8
Alteplase Active Control Group2.3
Percentage of Participants With Barthel Index Score ≥95 Secondary · up to 90 days

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.

GroupValue95% CI
Tenecteplase Treatment Group75.7
Alteplase Active Control Group73.9
Percentage of Participants With Symptomatic Intracerebral Haemorrhage (sICH) Per European Cooperative Acute Stroke Study (ECASS) Ⅲ Definition During On-treatment Period Secondary · Up to 7 days.

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.

GroupValue95% CI
Tenecteplase Treatment Group1.2
Alteplase Active Control Group1.2
Percentage of Participants Who Died by Day 90 Secondary · up to 90 days

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

GroupValue95% CI
Tenecteplase Treatment Group4.6
Alteplase Active Control Group5.8
Percentage of Participants With Modified Rankin Scale (mRS) Score of 5 or 6 Secondary · At Day 90

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.

GroupValue95% CI
Tenecteplase Treatment Group6.8
Alteplase Active Control Group7.8

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs are reported for the on-treatment period from start of treatment until end of residual effect period, up to 7 days. All cause mortality was reported from start of treatment until death by any cause, up to 97 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Alteplase Active Control Group
Serious: 115/736 (16%)
Deaths: 44/736
Tenecteplase Treatment Group
Serious: 116/732 (16%)
Deaths: 34/732

Serious adverse events (76 terms)

ReactionSystemAlteplase Active Control G…Tenecteplase Treatment Group
Cerebral haemorrhageNervous system disorders
Cerebral infarctionNervous system disorders
Haemorrhagic transformation strokeNervous system disorders
Deep vein thrombosisVascular disorders
Cardiac failureCardiac disorders
Brain herniationInjury, poisoning and procedural complications
PneumoniaInfections and infestations
Haemorrhage intracranialNervous system disorders
Haemorrhagic cerebral infarctionNervous system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationInfections and infestations
Basal ganglia haemorrhageNervous system disorders
Brain oedemaNervous system disorders
Subarachnoid haemorrhageNervous system disorders
ComaNervous system disorders
Brain stem haemorrhageNervous system disorders
Carotid artery occlusionNervous system disorders
EpilepsyNervous system disorders
HemiparesisNervous system disorders
Transient ischaemic attackNervous system disorders
Acute myocardial infarctionCardiac disorders
Cardiac failure acuteCardiac disorders
Hepatic failureHepatobiliary disorders
Cerebellar haemorrhageNervous system disorders
Ischaemic cerebral infarctionNervous system disorders
Other adverse events (9 terms — click to expand)

ReactionSystemAlteplase Active Control G…Tenecteplase Treatment Group
ConstipationGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
HyperhomocysteinaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
HypoproteinaemiaMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders

Most-reported serious reactions: Cerebral haemorrhage, Cerebral infarction, Haemorrhagic transformation stroke, Deep vein thrombosis, Cardiac failure, Brain herniation, Pneumonia, Haemorrhage intracranial.

Data from ClinicalTrials.gov NCT04915729 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial.
    Meng X, Li S, Dai H, Lu G, et al · · 2024 · cited 54× · PMID 39264623 · DOI 10.1001/jama.2024.14721
  2. Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies.
    Desilles JP, Di Meglio L, Delvoye F, Maïer B, et al · · 2022 · cited 21× · PMID 35873787 · DOI 10.3389/fneur.2022.870331
  3. 11th European Stroke Organisation Conference Abstracts - 21-23 May 2025, Helsinki, Finland.
    · 2025 · cited 3× · PMID 40726475 · DOI 10.1177/23969873251329993
  4. Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study.
    Meng X, Li S, Dai H, Lu G, et al · · 2024 · PMID 41585404 · DOI 10.1161/svin.124.001363

Verify or expand the search:

Other trials of tenecteplase

Trials testing the same drug.

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Other Boehringer Ingelheim trials

Trials by the same sponsor.

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