Platelet Dysfunction Due to DrugsPhase 1/2TWISTNCT04206176
The Effects of loW Dose tIcagrelor on Platelet Function Testing in Patients With Stable Coronary arTery Disease
A Phase 1/2 study testing Ticagrelor in people with Platelet Dysfunction Due to Drugs, run by The University of The West Indies at 1 site in Trinidad and Tobago.
Trial summary
This study aims to assess the effects of low dose ticagrelor on platelet function testing in patients with stable coronary artery disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Platelet Dysfunction Due to Drugs
- What is being tested?
- Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteTrinidad and Tobago
- Study dates
- 1 Oct 2019to 31 Mar 2020
- Phase
- Phase 1/2
- 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
- between 18 and 74 years of age,
- have stable coronary artery disease, already on DAPT with aspirin and clopidogrel for at least 6 months,
- not on any physician-prescribed medications or complementary/alternative therapies,
Who cannot join
- presence of active internal bleeding or history of bleeding diathesis or clinical findings associated with an increased risk of bleeding,
- history of ischemic or hemorrhagic stroke, transient ischemic attack, intracranial neoplasm, arteriovenous malformation, or aneurysm,
- history of clinical and/or hemodynamic instability,
- within 1 month of placement of a bare-metal stent,
- within 30 days of coronary artery bypass graft surgery or PCI without a stent placed,
- planned coronary revascularization,
Show all 15Show fewer
- treatment with fibrin-specific fibrinolytic therapy <24 h or non-fibrin-specific fibrinolytic therapy <48 h,
- use of an oral anticoagulation agent or international normalized ratio >1.5,
- body weight <60 kg,
- age >75 years,
- hemoglobin <10 g/dL,
- platelet count <100×106/μL,
- creatinine >2 mg/dL,
- hepatic enzymes >2.5 times the upper limit of normal,
- pregnancy and/or lactation.
Trial locations and contacts
1 site in 1 country.
Trinidad and Tobago1 site
The University of the West Indies
Saint Augustine, North, 000000
About this study
Official title: The Effects of loW Dose tIcagrelor on Platelet Function Testing in Patients With Stable Coronary arTery Disease: TWIST Trial
This study aims to assess the effects of low dose ticagrelor on platelet function testing in patients with stable coronary artery disease.
Read the detailed description
Dual antiplatelet therapy with aspirin and clopidogrel represents the standard of care for the prevention of recurrent ischemic events in patients undergoing percutaneous coronary intervention (PCI). For more than 20 years, dual antiplatelet therapy with aspirin and Clopidogrel has remained the cornerstone of treatment for patients with acute coronary syndrome (ACS). However, some patients have impaired clopidogrel response and thus persist with high on-treatment platelet reactivity (HPR) resulting in an increased risk of atherothrombotic events. The boxed warning added to the clopidogrel label underscoring the potential risk of adverse cardiovascular outcomes among patients with a "poor metabolizer" genotype and advocating the use of other antiplatelet medications or alternative dosing strategies for these patients has led to investigations of treatment options associated with more optimal platelet inhibition. These include switching to a novel generation P2Y12 inhibitor (e.g. prasugrel or ticagrelor).
Ticagrelor is an antagonist of the P2Y12 receptor. The drug was approved for use in the European Union by the European Medicines Agency on December 3, 2010. The drug was approved by the US Food and Drug Administration on July 20, 2011. The FDA indication for ticagrelor is a reduction of the rate of cardiovascular death, myocardial infarction (MI), and stroke in people with an acute coronary syndrome or history of myocardial infarction.
According to ESC 2017 guidelines, ticagrelor is the first-option treatment in patients with acute coronary syndrome with or without ST-segment elevation, irrespective of treatment strategy (invasive or non-invasive) - IB level of evidence. Furthermore, the 2017 ESC Focused Update on Duration of Dual Antiplatelet Therapy allows physicians to administer ticagrelor to patients with stable coronary artery disease undergoing percutaneous coronary intervention after taking thrombotic and hemorrhagic risk into consideration.
In healthy Chinese subjects, low-dose ticagrelor produced an antiplatelet efficacy similar to that of standard-dose ticagrelor, which was faster and more potent than the effect of clopidogrel. In the East Asian population, there is limited evidence available to date that compares low versus standard doses of ticagrelor to evaluate the clinical efficacy and safety. Larger and longer duration studies are warranted to more closely examine the appropriateness of lower doses of ticagrelor in this population.
The investigators postulate that inhibition of platelet aggregation in response to low dose Ticagrelor as opposed to the standard dose is non-inferior to that of Clopidogrel.
- Conditions
- Platelet Dysfunction Due to Drugs
- Being tested
- Ticagrelor
- Keywords
- antiplatelet drugs, clopidogrel, ticagrelor, high on-treatment platelet reactivity, platelet function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called Low Dose Ticagrelor
Ticagrelor 45mg twice daily per oral administration
| Study group | Role | What they receive |
|---|---|---|
| Single group crossover | Experimental | The patients who are on a maintenance dose of clopidogrel 75mg once daily will be transitioned to ticagrelor 45mg twice daily after which they will be tested. Receives: Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical effectiveness and safety of low ticagrelor as compared to standard dose clopidogrel based on platelet reaction units (PRU).
Platelet Reaction Units of low dose ticagrelor vs. standard dose clopidogrel
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start1 Oct 2019
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
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 Platelet Dysfunction Due to DrugsStudies 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 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single, group crossover from clopidogrel to low dose ticagrelor.
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of The West Indies
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Naveen Seecheran, The University of The West Indies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206176
- Sponsor's protocol ID
- CEC1152/06/19
- Acronym
- TWIST
- Status last verified
- May 2020
- First submitted
- 28 Nov 2019
- Last updated
- 21 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Seecheran N, Boodhai B, Maharaj A, Ramdeen A, Debideen N, Ochalal V, Singh R, Seecheran R, Seecheran V, Persad S, Abdullah H, Peram L, Motilal S, Tello-Montoliu A, Schneider D. The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study. Cardiol Ther. 2020 Dec;9(2):493-503. doi: 10.1007/s40119-020-00195-2. Epub 2020 Aug 6.
PubMed 32766961
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of loW Dose tIcagrelor on Platelet Function Testing in Patients With Stable Coronary arTery Disease: TWIST Trial
- ClinicalTrials.gov ID
- NCT04206176
- Acronym / sponsor ID
- TWIST / CEC1152/06/19
- Conditions
- Platelet Dysfunction Due to Drugs
- Keywords
- antiplatelet drugs, clopidogrel, ticagrelor, high on-treatment platelet reactivity, platelet function
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The University of The West IndiesUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 20 Dec 2019 (actual)
- 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.
This study aims to assess the effects of low dose ticagrelor on platelet function testing in patients with stable coronary artery disease.
Detailed description
Dual antiplatelet therapy with aspirin and clopidogrel represents the standard of care for the prevention of recurrent ischemic events in patients undergoing percutaneous coronary intervention (PCI). For more than 20 years, dual antiplatelet therapy with aspirin and Clopidogrel has remained the cornerstone of treatment for patients with acute coronary syndrome (ACS). However, some patients have impaired clopidogrel response and thus persist with high on-treatment platelet reactivity (HPR) resulting in an increased risk of atherothrombotic events. The boxed warning added to the clopidogrel label underscoring the potential risk of adverse cardiovascular outcomes among patients with a "poor metabolizer" genotype and advocating the use of other antiplatelet medications or alternative dosing strategies for these patients has led to investigations of treatment options associated with more optimal platelet inhibition. These include switching to a novel generation P2Y12 inhibitor (e.g. prasugrel or ticagrelor).
Ticagrelor is an antagonist of the P2Y12 receptor. The drug was approved for use in the European Union by the European Medicines Agency on December 3, 2010. The drug was approved by the US Food and Drug Administration on July 20, 2011. The FDA indication for ticagrelor is a reduction of the rate of cardiovascular death, myocardial infarction (MI), and stroke in people with an acute coronary syndrome or history of myocardial infarction.
According to ESC 2017 guidelines, ticagrelor is the first-option treatment in patients with acute coronary syndrome with or without ST-segment elevation, irrespective of treatment strategy (invasive or non-invasive) - IB level of evidence. Furthermore, the 2017 ESC Focused Update on Duration of Dual Antiplatelet Therapy allows physicians to administer ticagrelor to patients with stable coronary artery disease undergoing percutaneous coronary intervention after taking thrombotic and hemorrhagic risk into consideration.
In healthy Chinese subjects, low-dose ticagrelor produced an antiplatelet efficacy similar to that of standard-dose ticagrelor, which was faster and more potent than the effect of clopidogrel. In the East Asian population, there is limited evidence available to date that compares low versus standard doses of ticagrelor to evaluate the clinical efficacy and safety. Larger and longer duration studies are warranted to more closely examine the appropriateness of lower doses of ticagrelor in this population.
The investigators postulate that inhibition of platelet aggregation in response to low dose Ticagrelor as opposed to the standard dose is non-inferior to that of Clopidogrel.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single, group crossover from clopidogrel to low dose ticagrelor.
| Arm | Type | Receives |
|---|---|---|
| Single group crossover | Experimental | Drug: TicagrelorThe patients who are on a maintenance dose of clopidogrel 75mg once daily will be transitioned to ticagrelor 45mg twice daily after which they will be tested. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- between 18 and 74 years of age,
- have stable coronary artery disease, already on DAPT with aspirin and clopidogrel for at least 6 months,
- not on any physician-prescribed medications or complementary/alternative therapies,
Key exclusion criteria (15 listed)
- presence of active internal bleeding or history of bleeding diathesis or clinical findings associated with an increased risk of bleeding,
- history of ischemic or hemorrhagic stroke, transient ischemic attack, intracranial neoplasm, arteriovenous malformation, or aneurysm,
- history of clinical and/or hemodynamic instability,
- within 1 month of placement of a bare-metal stent,
- within 30 days of coronary artery bypass graft surgery or PCI without a stent placed,
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 |
|---|---|---|
| TicagrelorAlso: Low Dose TicagrelorTicagrelor 45mg twice daily per oral administration | Drug | Single group crossover |
Primary outcome
Clinical effectiveness and safety of low ticagrelor as compared to standard dose clopidogrel based on platelet reaction units (PRU).
Time frame: 2 weeks
Platelet Reaction Units of low dose ticagrelor vs. standard dose clopidogrel
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 21 May 2020.
- Derived from this study: PubMed 32766961Seecheran N, Boodhai B, Maharaj A, Ramdeen A, Debideen N, Ochalal V, Singh R, Seecheran R, Seecheran V, Persad S, Abdullah H, Peram L, Motilal S, Tello-Montoliu A, Schneider D. The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study. Cardiol Ther. 2020 Dec;9(2):493-503. doi: 10.1007/s40119-020-00195-2. Epub 2020 Aug 6.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ticagrelor in people with Platelet Dysfunction Due to Drugs, run by The University of The West Indies at 1 site in Trinidad and Tobago.
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 3 inclusion and 15 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 21 May 2020. 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 Trinidad and Tobago. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Clinical effectiveness and safety of low ticagrelor as compared to standard dose clopidogrel based on platelet reaction units (PRU). (time frame: 2 weeks). 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 NCT04206176, 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 21 May 2020.