StrokePhase 3TARDISNCT01661322
Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke
A Phase 3 study testing Aspirin, Dipyradimole, Clopidogrel in people with Stroke, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
The risk of recurrence is greatest immediately after stroke or Transient Ischaemic Attack (TIA). Existing prevention strategies (antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Aspirin, Dipyradimole, Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,096 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2009to Sep 2017
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults at high risk of recurrent ischaemic stroke:
- Age ≥ 50 years
- Within 48 hours of ictus (24-48 hours if thrombolysed)
- TIA with limb weakness and/or dysphasia lasting between 10 minutes and < 24 hours with no residual symptoms and presenting with any of the following
- ABCD2 score > 4, or
- Crescendo TIA or
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- Already on dual antiplatelet therapy
- Note: Neuroimaging is not necessary for transient ischaemic attack. Crescendo TIA is > 1 TIA in one week and the onset time of last TIA is taken as time of ictus.
- Ischaemic non cardioembolic stroke presenting with any of the following
- Ongoing limb weakness and/or dysphasia of more than one hour duration
- Resolved limb weakness of more than one hour duration with ongoing facial weakness
- Ongoing isolated hemianopia of more than 1 hour duration with positive neuroimaging evidence to support the index event (e.g. ischaemic stroke in occipital lobe)
- Resolved limb weakness and/or dysphasia between 24-48 hours after index event onset
- Note: Neuroimaging is essential for ischaemic stroke to exclude intracranial haemorrhage and/or non stroke diagnosis
- Informed consent from participant. If the participant is unable to give meaningful consent e.g. due to dysphasia, confusion, or reduced conscious level, proxy consent may be obtained from a relative, carer or legal representative.
Who cannot join
- Age < 50
- Isolated sensory symptoms or vertigo/dizziness or facial weakness
- Isolated hemianopia without positive neuroimaging evidence
- Intracranial haemorrhage
- Baseline neuroimaging showing parenchymal haemorrhagic transformation (PH I/II) of infarct, subarachnoid haemorrhage or other non ischaemic cause for symptoms
- Presumed cardioembolic stroke (e.g. history or current AF, myocardial infarction within 3 months)
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- Participants with contraindications to, or intolerance of, aspirin, clopidogrel or dipyridamole.
- Participants with definite need for treatment with aspirin, clopidogrel or dipyridamole individually or in combination (e.g. aspirin and clopidogrel for recent MI/acute coronary syndrome)
- Participant has taken clopidogrel or dipyridamole after the index event but prior to randomisation (aspirin is allowed between ictus onset and randomisation)
- Definite need for full dose oral (e.g. warfarin, dabigatran) or medium to high dose parenteral (e.g. heparin) anti-coagulation. NB Low dose heparin for DVT prophylaxis is allowed
- Definite need for glycoprotein IIb-IIIa inhibitors
- Received thrombolysis within the last 24 hours
- No enteral access
- Pre-morbid dependency (mRS > 2).
- Severe high BP (BP > 185/110 mmHg).
- Haemoglobin less than 10g/dL
- Platelet count more than 600 x 109 /L or less than 100 x 109 /L
- White cell count more than 30 x 109 /L or less than 3.5 x 109 /L
- Major bleeding within 1 year (e.g. peptic ulcer, intracerebral haemorrhage).
- Planned surgery during 3 month follow-up (e.g. carotid endarterectomy)
- Concomitant STEMI or NSTEMI.
- Stroke secondary to a procedure (e.g. carotid or coronary intervention)
- Coma (GCS < 8)
- Non-stroke life expectancy < 6 months
- Dementia
- Participation in another drug or devices trial concurrently or within 30 days. (participants may take part in observational studies or non-drug or devices trials)
- Geographical or other factors that may interfere with follow-up e.g. no fixed address or telephone contact number, not registered with a GP, or overseas visitor.
- Females of childbearing potential, pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Nottingham University Hospitals NHS Trust
Nottingham
About this study
Official title: Safety and Efficacy of Intensive Versus Guideline Antiplatelet Therapy in High Risk Patients With Recent Ischaemic Stroke or Transient Ischaemic Attack: a Randomised Controlled Trial
The risk of recurrence is greatest immediately after stroke or Transient Ischaemic Attack (TIA). Existing prevention strategies (antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Dual antiplatelet therapy - aspirin \& clopidogrel (AC) for IHD, aspirin \& dipyridamole (AD) for stroke, is superior to aspirin monotherapy. The investigators hypothesise that triple antiplatelet therapy (ACD) will be superior to AD in patients at high-risk of recurrence, providing bleeding does not become excessive.
Design: TARDIS is a multicentre, parallel-group, prospective, randomised, open-label, blinded-endpoint, controlled trial. In the start-up phase, the investigators will assess over 3 years the safety, tolerability and feasibility of intensive therapy (ACD) versus guideline therapy (AD) given for 1 month in 750 patients with acute stroke/TIA. The main phase will then assess the safety and efficacy of ACD in up to 3500 patients. The primary outcome is ordinal stroke (fatal/severe non-fatal/mild/TIA/none) at 90 days. Secondary outcomes include death, MI, vascular events, function, bleeding, serious adverse events; sub-studies will assess cerebral emboli and platelet function.
Read the detailed description
2.1 Purpose To perform a randomised trial assessing the efficacy, safety and tolerability of intensive antiplatelet therapy (Asp+Dip+Clop) versus guideline antiplatelet therapy (Asp+Dip or Clop) in patients with recent ischaemic stroke or TIA and who are at high risk of recurrence.
2.2 Primary Objective To assess ordinal stroke severity at 90 days after short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
2.3 Secondary Objectives
- To assess the safety of short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
- To further assess, in high risk patients with stroke/TIA, whether: ii. it is feasible to administer intensive therapy acutely and is tolerable to take for 1 month, iii. intensive therapy is superior in respect of surrogate markers such as platelet function. iv. intensive therapy improves functional outcome
- Conditions
- Stroke
- Being tested
- Aspirin, Dipyradimole, Clopidogrel
- Keywords
- Acute ischaemic stroke, TIA
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aspirin, Dipyradimole, ClopidogrelDrug
Also called Aspirin, Dipyradimole, Clopidogrel
Participants in the intensive antiplatelet group will receive Asp+Dip+Clop triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days.
| Study group | Role | What they receive |
|---|---|---|
| Intensive antiplatelet therapy | Active comparator | Participants in the intensive antiplatelet group will receive Aspirin+Dipyridamole+Clopidogrel triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days. Receives: Drug: Aspirin, Dipyradimole, Clopidogrel |
| Guideline antiplatelet therapy | No intervention | This may be one or two antiplatelet drugs, as per standard treatment. Clopidogrel or aspirin and dipyridamole. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is ordinal stroke severity at 90 days
5-level ordinal stroke and TIA scale with stroke ordered by its severity using the modified Rankin Scale (mRS): fatal stroke / severe non-fatal stroke (mRS 2-5) / mild stroke (mRS 0,1) / TIA / no stroke-TIA, measured at 90 days.; this approach allows for smaller sample sizes compared to binary outcomes such as stroke/no stroke
Measured: 90 days
Secondary outcomes (4)
Safety
Days 7 and 35 Full blood count by local investigator
Days 7, 35 and 90:
Ordinal bleeding (fatal/major/moderate/minor/none42) as adjudicated by an independent blinded panel; death; binary major bleeding (fatal, symptomatic, causing fall in haemoglobin of ≥2g/l, or leading to transfusion of ≥2 units of blood/red cells);45 binary minor bleeding (e.g. bruising) binary bleeding; all bleeding, symptomatic intracerebral haemorrhage, major extracranial bleeding, binary serious adverse events, ordinal adverse events (fatal/serious/other/none42); thrombotic thrombocytopenic purpura; granulocytopenia.
Measured: 90 days
Serious adverse events
Measured: 90 Days
Death
Measured: 90 days
Platelet function.
Days 7 and 35 Full blood count by local investigator
Days 7, 35 and 90:
Ordinal bleeding (fatal/major/moderate/minor/none42) as adjudicated by an independent blinded panel; death; binary major bleeding (fatal, symptomatic, causing fall in haemoglobin of ≥2g/l, or leading to transfusion of ≥2 units of blood/red cells);45 binary minor bleeding (e.g. bruising) binary bleeding; all bleeding, symptomatic intracerebral haemorrhage, major extracranial bleeding, binary serious adverse events, ordinal adverse events (fatal/serious/other/none42); thrombotic thrombocytopenic purpura; granulocytopenia.
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startApr 2009
- Primary completionSep 2017
- Study completionSep 2017
Why it stopped: Trial reached a definitive answer ahead of full recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 3,096 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philip Bath, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661322
- Sponsor's protocol ID
- 08093
- Other IDs
- 2007-006749-42
- Acronym
- TARDIS
- Status last verified
- Jun 2018
- First submitted
- 23 Jul 2012
- Last updated
- 11 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Intensive Versus Guideline Antiplatelet Therapy in High Risk Patients With Recent Ischaemic Stroke or Transient Ischaemic Attack: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT01661322
- Acronym / sponsor ID
- TARDIS / 08093
- Conditions
- Stroke
- Keywords
- Acute ischaemic stroke, TIA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial reached a definitive answer ahead of full recruitment.
- Enrolment
- 3,096 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 9 Aug 2012 (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 risk of recurrence is greatest immediately after stroke or Transient Ischaemic Attack (TIA). Existing prevention strategies (antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Dual antiplatelet therapy - aspirin \& clopidogrel (AC) for IHD, aspirin \& dipyridamole (AD) for stroke, is superior to aspirin monotherapy. The investigators hypothesise that triple antiplatelet therapy (ACD) will be superior to AD in patients at high-risk of recurrence, providing bleeding does not become excessive.
Design: TARDIS is a multicentre, parallel-group, prospective, randomised, open-label, blinded-endpoint, controlled trial. In the start-up phase, the investigators will assess over 3 years the safety, tolerability and feasibility of intensive therapy (ACD) versus guideline therapy (AD) given for 1 month in 750 patients with acute stroke/TIA. The main phase will then assess the safety and efficacy of ACD in up to 3500 patients. The primary outcome is ordinal stroke (fatal/severe non-fatal/mild/TIA/none) at 90 days. Secondary outcomes include death, MI, vascular events, function, bleeding, serious adverse events; sub-studies will assess cerebral emboli and platelet function.
Detailed description
2.1 Purpose To perform a randomised trial assessing the efficacy, safety and tolerability of intensive antiplatelet therapy (Asp+Dip+Clop) versus guideline antiplatelet therapy (Asp+Dip or Clop) in patients with recent ischaemic stroke or TIA and who are at high risk of recurrence.
2.2 Primary Objective To assess ordinal stroke severity at 90 days after short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
2.3 Secondary Objectives
- To assess the safety of short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
- To further assess, in high risk patients with stroke/TIA, whether: ii. it is feasible to administer intensive therapy acutely and is tolerable to take for 1 month, iii. intensive therapy is superior in respect of surrogate markers such as platelet function. iv. intensive therapy improves functional outcome
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive antiplatelet therapy | Active comparator | Drug: Aspirin, Dipyradimole, ClopidogrelParticipants in the intensive antiplatelet group will receive Aspirin+Dipyridamole+Clopidogrel triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days. |
| Guideline antiplatelet therapy | No intervention | –This may be one or two antiplatelet drugs, as per standard treatment. Clopidogrel or aspirin and dipyridamole. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 50 years
- Within 48 hours of ictus (24-48 hours if thrombolysed)
- TIA with limb weakness and/or dysphasia lasting between 10 minutes and < 24 hours with no residual symptoms and presenting with any of the following
- Note: Neuroimaging is not necessary for transient ischaemic attack. Crescendo TIA is > 1 TIA in one week and the onset time of last TIA is taken as time of ictus.
- Ischaemic non cardioembolic stroke presenting with any of the following
Key exclusion criteria (28 listed)
- Age < 50
- Isolated sensory symptoms or vertigo/dizziness or facial weakness
- Isolated hemianopia without positive neuroimaging evidence
- Intracranial haemorrhage
- Baseline neuroimaging showing parenchymal haemorrhagic transformation (PH I/II) of infarct, subarachnoid haemorrhage or other non ischaemic cause for symptoms
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 |
|---|---|---|
| Aspirin, Dipyradimole, ClopidogrelAlso: Aspirin, Dipyradimole, ClopidogrelParticipants in the intensive antiplatelet group will receive Asp+Dip+Clop triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days. | Drug | Intensive antiplatelet therapy |
Primary outcome
The primary outcome is ordinal stroke severity at 90 days
Time frame: 90 days
5-level ordinal stroke and TIA scale with stroke ordered by its severity using the modified Rankin Scale (mRS): fatal stroke / severe non-fatal stroke (mRS 2-5) / mild stroke (mRS 0,1) / TIA / no stroke-TIA, measured at 90 days.; this approach allows for smaller sample sizes compared to binary outcomes such as stroke/no stroke
4 secondary outcomes
Safety
Time frame: 90 days
Serious adverse events
Time frame: 90 Days
Death
Time frame: 90 days
Platelet function.
Time frame: 90 Days
Results and safety
The study was stopped early (reason given: Trial reached a definitive answer ahead of full recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2018.
- TARDIS Trial WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Philip Bath principal investigator
University of Nottingham
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 Aspirin, Dipyradimole, Clopidogrel in people with Stroke, run by University of Nottingham 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 15 inclusion and 28 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: stopped early, as of the sponsor's last update on 11 Jun 2018. 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 was stopped early (reason given: Trial reached a definitive answer ahead of full recruitment.). Results are not available in the source record.
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?
The primary outcome is ordinal stroke severity at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2018.