Trial Outcomes & Findings for A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion (NCT NCT02398656)

Last Updated: 2025-01-31

Results Overview

Analysis will be a responder analysis where return to baseline level of neurological functioning is defined as follows: If pre-morbid mRS is 0-1 then mRS 0-1 at 90 days is a good outcome. If pre-morbid mRS is 2 then mRS 0-2 is a good outcome. Pre-morbid mRS is assessed using the structured mRS prior to randomization. Outcomes at 90 days will be assessed by an individual blinded to the treatment assignment. The 90day mRS will be rated using the structured mRS questionnaire . The 90 day mRS will be completed in person where possible and by telephone otherwise. The structured questionnaire has been showed to improve reliability in assessing the mRS both in person and by telephone. This is a scale from 0-6. Higher scores mean a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1274 participants

Primary outcome timeframe

90 Days

Results posted on

2025-01-31

Participant Flow

Participant milestones

Participant milestones
Measure	Tenecteplase (tNK) Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Overall Study STARTED	637	637
Overall Study COMPLETED	454	432
Overall Study NOT COMPLETED	183	205

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tenecteplase (tNK) n=432 Participants Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) n=452 Participants Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.	Total n=884 Participants Total of all reporting groups
Age, Continuous	72 years n=5 Participants	72 years n=7 Participants	72 years n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants	180 Participants n=7 Participants	368 Participants n=5 Participants
Sex: Female, Male Male	244 Participants n=5 Participants	272 Participants n=7 Participants	516 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	427 Participants n=5 Participants	443 Participants n=7 Participants	870 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Asian	40 Participants n=5 Participants	42 Participants n=7 Participants	82 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	371 Participants n=5 Participants	382 Participants n=7 Participants	753 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	16 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: 90 Days

Outcome measures

Outcome measures
Measure	Tenecteplase (tNK) n=432 Participants Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) n=452 Participants Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Number of Participants With Return to Baseline Neurological Functioning Measured by the Modified Rankin Scale (mRS)	309 Participants	338 Participants

SECONDARY outcome

Timeframe: 90 days

Pre-morbid mRS is assessed using the structured mRS prior to randomization. Outcomes will be assessed by an individual blinded to the treatment assignment. The 90day mRS will be rated using the structured mRS questionnaire . The 90 day mRS will be completed in person where possible and by telephone otherwise. The structured questionnaire has been showed to improve reliability in assessing the mRS both in person and by telephone. This is a scale from 0-6. Higher scores mean a worse outcome. mRS 0-1 represents excellent functional outcome.

Outcome measures

Outcome measures
Measure	Tenecteplase (tNK) n=432 Participants Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) n=452 Participants Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Number of Participants With Modified Rankin Score (mRS) 0-1 at 90 Days	298 Participants	321 Participants

Adverse Events

Tenecteplase (tNK)

Serious events: 16 serious events

Other events: 35 other events

Deaths: 20 deaths

Control (Antiplatelet Agents)

Serious events: 2 serious events

Other events: 33 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Tenecteplase (tNK) n=435 participants at risk；n=432 participants at risk Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) n=452 participants at risk Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Nervous system disorders Symptomatic Intracerebral hemorrhage	3.7% 16/432 • Number of events 16 • Adverse events were collected from randomization to Day 5 or discharge ( whichever was sooner). SAE's were collected to the Day 90 assessment completion. AEs and SAE's were collected from the beginning of the trial until the last Day 90 assessment was completed. AE and SAE definitions are as per GCP requirements.	0.44% 2/452 • Number of events 2 • Adverse events were collected from randomization to Day 5 or discharge ( whichever was sooner). SAE's were collected to the Day 90 assessment completion. AEs and SAE's were collected from the beginning of the trial until the last Day 90 assessment was completed. AE and SAE definitions are as per GCP requirements.

Other adverse events

Other adverse events
Measure	Tenecteplase (tNK) n=435 participants at risk；n=432 participants at risk Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase. Tenecteplase: TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.	Control (Antiplatelet Agents) n=452 participants at risk Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization. Antiplatelet treatment: Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Nervous system disorders Stroke Progression	8.0% 35/435 • Number of events 35 • Adverse events were collected from randomization to Day 5 or discharge ( whichever was sooner). SAE's were collected to the Day 90 assessment completion. AEs and SAE's were collected from the beginning of the trial until the last Day 90 assessment was completed. AE and SAE definitions are as per GCP requirements.	7.3% 33/452 • Number of events 33 • Adverse events were collected from randomization to Day 5 or discharge ( whichever was sooner). SAE's were collected to the Day 90 assessment completion. AEs and SAE's were collected from the beginning of the trial until the last Day 90 assessment was completed. AE and SAE definitions are as per GCP requirements.

Additional Information

Dr. Shelagh Coutts

University of Calgary

Phone: 4039444286

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place