Clinical Trial Results:
Multi-Centre, prosepective randomised open label, blinded-endpoint (PROBE) controlled trial of thrombolysis with low dose Tenecteplase (TNK-tPA) versus standard of care in the prevention of disability at 3 months in minor ischemic stroke with proven acute symptomatic occlusion.
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Summary
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EudraCT number |
2015-005469-22 |
Trial protocol |
AT IE ES FI |
Global end of trial date |
19 Jan 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Feb 2025
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First version publication date |
01 Feb 2025
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Other versions |
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Summary report(s) |
The Lancet TEMPO 2 2024 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TEMPO-2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02398656 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Calgary
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Sponsor organisation address |
2500 University Drive, Calgary, Canada, AB T2N 2T9
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Public contact |
Dr Shelagh B. Coutts, University of Calgary, 1 4039441594, scoutts@ucalgary.ca
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Scientific contact |
Dr Shelagh B. Coutts, University of Calgary, 1 4039441594, scoutts@ucalgary.ca
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Jan 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jan 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Jan 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective: to demonstrate the efficacy of using TNK-tPA to treat minor ischemic stroke with proven arterial occlusion.
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Protection of trial subjects |
Follow up at 90 days
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Background therapy |
Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 514
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Country: Number of subjects enrolled |
Australia: 168
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Country: Number of subjects enrolled |
New Zealand: 1
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Country: Number of subjects enrolled |
Singapore: 1
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Country: Number of subjects enrolled |
Brazil: 19
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Country: Number of subjects enrolled |
Spain: 64
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Country: Number of subjects enrolled |
United Kingdom: 83
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Country: Number of subjects enrolled |
Austria: 20
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Country: Number of subjects enrolled |
Finland: 13
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Country: Number of subjects enrolled |
Ireland: 3
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Worldwide total number of subjects |
886
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EEA total number of subjects |
100
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
281
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From 65 to 84 years |
489
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85 years and over |
116
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Recruitment
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Recruitment details |
Eligible patients with minor acute ischaemic stroke and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The principles of patient selection are based upon the broad criteria of: a. TIAor minor stroke presentation with a diagnosis of an ischemic stroke syndrome b. Imaging proof of an intracranial occlusion or a perfusion abnormality relevant to the presenting symptoms c. No region of well-defined hypodensity on the NCCT | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | ||||||||||||||||||||||||
Roles blinded |
Assessor [1] | ||||||||||||||||||||||||
Blinding implementation details |
Blinding of the outcome assessment at 90 days
was ensured by the sites by having a person who was blinded to treatment
allocation and not involved in the acute treatment period conduct the assessment
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention Arm | ||||||||||||||||||||||||
Arm description |
In the intervention group TNK-tPA is given as a single, intravenous bolus (0.25mg/Kg) immediately upon randomization. Maximum dose 50mg. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Tenecteplase
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Investigational medicinal product code |
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Other name |
TNK-tPA
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
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 5-10 seconds as per the standard manufacturers’ instructions for use.
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Arm title
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Control Arm | ||||||||||||||||||||||||
Arm description |
Patients will be treated with standard of care based antiplatelet treatment | ||||||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Blinding of the outcome assessment at 90 days will be ensured at the site by having a person who was blinded to treatment allocation and not involved in the acute treatment period conduct the assessment. This is a per the Protocol |
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| Notes [2] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero. Justification: 4 pts from the control arm crossed over to thrombolysis and were given intravenous alteplase 1 pt from the treatment arm crossed over to the control arm and was given aspirin plus clopidogrel |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention Arm
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Reporting group description |
In the intervention group TNK-tPA is given as a single, intravenous bolus (0.25mg/Kg) immediately upon randomization. Maximum dose 50mg. | ||
Reporting group title |
Control Arm
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Reporting group description |
Patients will be treated with standard of care based antiplatelet treatment | ||
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End point title |
Return to baseline neurological functioning as measured by the mRS [1] | ||||||||||||
End point description |
Primary outcome: Return to baseline neurological functioning as measured by the mRS.
Analysis will be a responder analysis where return to baseline level of neurological functioning using a variation of the sliding dichotomy modified Rankin Scale score outcome, 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.
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End point type |
Primary
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End point timeframe |
90 days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary outcome: Return to baseline neurological functioning as measured by the mRS. Analysis will be a responder analysis where return to baseline level of neurological functioning using a variation of the sliding dichotomy modified Rankin Scale score outcome, 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. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse events were collected through the first 5 days of trial participation.
Serious adverse events (SAEs) were collected for the full 90-day trial period.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Intervention Arm
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Reporting group description |
In the intervention group TNK-tPA is given as a single, intravenous bolus (0.25mg/Kg) immediately upon randomization. Maximum dose 50mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control Arm
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Reporting group description |
Patients will be treated with standard of care based antiplatelet treatment – choice at the discretion of the investigator. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Frequency threshold was not applicable. Simple AEs not reported. Study only reported serious AEs. |
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| Notes [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Numbers are equal [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Number are equal |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Nov 2018 |
1. Further clarification was added on enrollment of participants who have had recent treatment with a low molecular weight heparin or direct oral anticoagulants (normal and impaired renal function)
2. Amended protocol indicated that where standard hospital supplies of tenecteplase are used there is no requirement for sites to perform temperature monitoring.
Non-substantial changes are as follows:
1. Novel anticoagulants are now termed ‘direct oral anticoagulants’.
2. Clarification that off-the shelf tenecteplase will be used in the study and that training will be provided on the preparation and administration of tenecteplase.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/38768626 |
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