Ischemic StrokePhase 3ATTEST2NCT02814409
Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis
A Phase 3 study testing Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase and Intravenous Tenecteplase in people with Ischemic Stroke, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
Trial summary
The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90? Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase and Intravenous Tenecteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,858 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Dec 2016to 10 Jan 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Eligible for intravenous thrombolysis.
- Male or non-pregnant female ≥18 years of age.
- <4.5h after symptom onset.
- Consent of patient or legal representative.
- Independent prior to the stroke (estimated modified Rankin Scale 0-2).
Who cannot join
- Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (> 2 minutes) within the previous 14 days; Acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; Active peptic ulceration; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose <2 mmol/l or >18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) >1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be >12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged.
- Any major medical condition likely to limit survival to day 90.
- Unavailable for day 90 follow-up.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?
- Conditions
- Ischemic Stroke
- Being tested
- Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase, Intravenous Tenecteplase
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous recombinant tissue plasminogen activator (rtPA) AlteplaseDrug
Also called Actilyse, recombinant tissue plasminogen activator (rtPA)
IV Alteplase 0.9mg/kg (max 90mg) bolus + 1h infusion
Intravenous TenecteplaseDrug
Also called Metalyse, TNK
IV Tenecteplase 0.25mg/kg (max 25mg) single bolus
| Study group | Role | What they receive |
|---|---|---|
| Alteplase - standard care | Active comparator | Alteplase 0.9 mg/kg with 10% of the total dose administered as an initial intravenous bolus and remaining 90% of the total dose administered as an intravenous infusion over 1 hour (maximum dose 90mg). Receives: Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase |
| Tenecteplase | Experimental | Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg). Receives: Drug: Intravenous Tenecteplase |
What is being measured
The primary outcome is the main question the study is designed to answer.
modified Rankin Scale
modified Rankin Scale (mRS) at day 90, determined by the Rankin Focused Assessment (RFA) method using centralised telephone interview, analysed by ordinal distribution ("shift") analysis of the scores in intervention and control groups.
Measured: Day 90 (+/- 7)
Secondary outcomes (6)
Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).
Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).
Measured: Day 90 (+/- 7)
Independent recovery (modified Rankin Scale score 0-2 versus 3-6).
Independent recovery (modified Rankin Scale score 0-2 versus 3-6).
Measured: Day 90 (+/- 7)
Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s).
Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s).
Measured: 24 hours
Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)
Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)
Measured: Day 90 (+/- 7)
Barthel Index score
Barthel Index score
Measured: Day 90 (+/- 7)
Need for thrombectomy
Need for thrombectomy
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2016 (estimated)
- Study start15 Dec 2016
- Primary completion31 Aug 2023
- Study completion10 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- None (open label)
- Enrolment
- 1,858 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, University of Edinburgh, Oxford University Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- Keith Muir, MD, FRCP, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02814409
- Sponsor's protocol ID
- GN14NE598
- Acronym
- ATTEST2
- Status last verified
- Jun 2024
- First submitted
- 23 Jun 2016
- Last updated
- 13 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Muir KW, Ford GA, Ford I, Wardlaw JM, McConnachie A, Greenlaw N, Mair G, Sprigg N, Price CI, MacLeod MJ, Dima S, Venter M, Zhang L, O'Brien E, Sanyal R, Reid J, Sztriha LK, Haider S, Whiteley WN, Kennedy J, Perry R, Lakshmanan S, Chakrabarti A, Hassan A, Marigold R, Raghunathan S, Sims D, Bhandari M, Wiggam I, Rashed K, Douglass C; ATTEST-2 Investigators. Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol. 2024 Nov;23(11):1087-1096. doi: 10.1016/S1474-4422(24)00377-6.
PubMed 39424558
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
- ClinicalTrials.gov ID
- NCT02814409
- Acronym / sponsor ID
- ATTEST2 / GN14NE598
- Conditions
- Ischemic Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,858 participants (actual)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, University of Edinburgh, Oxford University Hospitals NHS Trust
- Study start
- 15 Dec 2016 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 27 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alteplase - standard care | Active comparator | Drug: Intravenous recombinant tissue plasminogen activator (rtPA) AlteplaseAlteplase 0.9 mg/kg with 10% of the total dose administered as an initial intravenous bolus and remaining 90% of the total dose administered as an intravenous infusion over 1 hour (maximum dose 90mg). |
| Tenecteplase | Experimental | Drug: Intravenous TenecteplaseTenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Eligible for intravenous thrombolysis.
- Male or non-pregnant female ≥18 years of age.
- <4.5h after symptom onset.
- Consent of patient or legal representative.
- Independent prior to the stroke (estimated modified Rankin Scale 0-2).
Key exclusion criteria (3 listed)
- Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (> 2 minutes) within the previous 14 days; Acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; Active peptic ulceration; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose <2 mmol/l or >18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) >1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be >12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged.
- Any major medical condition likely to limit survival to day 90.
- Unavailable for day 90 follow-up.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous recombinant tissue plasminogen activator (rtPA) AlteplaseAlso: Actilyse, recombinant tissue plasminogen activator (rtPA)IV Alteplase 0.9mg/kg (max 90mg) bolus + 1h infusion | Drug | Alteplase - standard care |
| Intravenous TenecteplaseAlso: Metalyse, TNKIV Tenecteplase 0.25mg/kg (max 25mg) single bolus | Drug | Tenecteplase |
Primary outcome
modified Rankin Scale
Time frame: Day 90 (+/- 7)
modified Rankin Scale (mRS) at day 90, determined by the Rankin Focused Assessment (RFA) method using centralised telephone interview, analysed by ordinal distribution ("shift") analysis of the scores in intervention and control groups.
6 secondary outcomes
Full neurological recovery (modified Rankin Scale 0-1 versus 2-6).
Time frame: Day 90 (+/- 7)
Independent recovery (modified Rankin Scale score 0-2 versus 3-6).
Time frame: Day 90 (+/- 7)
Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s).
Time frame: 24 hours
Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D)
Time frame: Day 90 (+/- 7)
Barthel Index score
Time frame: Day 90 (+/- 7)
Need for thrombectomy
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2024.
- Derived from this study: PubMed 39424558Muir KW, Ford GA, Ford I, Wardlaw JM, McConnachie A, Greenlaw N, Mair G, Sprigg N, Price CI, MacLeod MJ, Dima S, Venter M, Zhang L, O'Brien E, Sanyal R, Reid J, Sztriha LK, Haider S, Whiteley WN, Kennedy J, Perry R, Lakshmanan S, Chakrabarti A, Hassan A, Marigold R, Raghunathan S, Sims D, Bhandari M, Wiggam I, Rashed K, Douglass C; ATTEST-2 Investigators. Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol. 2024 Nov;23(11):1087-1096. doi: 10.1016/S1474-4422(24)00377-6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith Muir, MD, FRCP principal investigator
University of Glasgow
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase and Intravenous Tenecteplase in people with Ischemic Stroke, run by NHS Greater Glasgow and Clyde at 1 site in United Kingdom.
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 5 inclusion and 3 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 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
modified Rankin Scale (time frame: Day 90 (+/- 7)). 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 NCT02814409, which also lists 1 linked publication.
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 13 Jun 2024; AzTrials last refreshed its copy on 30 Oct 2026.