Acute Coronary SyndromePhase 2/3RAPID MANAGENCT02044146
A Pharmacodynamic Study of a Personalized Strategy for P2Y12 Inhibition Versus Ticagrelor in Reducing Ischemic and Bleeding Risk
A Phase 2/3 study testing Ticagrelor, Prasugrel, Clopidogrel in people with Acute Coronary Syndrome and Percutaneous Coronary Intervention, run by Ottawa Heart Institute Research Corporation at 2 sites in Canada.
Trial summary
In patients with heart attacks, the treatment of choice is to restore blood flow with percutaneous coronary intervention (PCI) (use of stents (metal meshes) to open blockages). After PCI, the standard drug treatment includes aspirin and clopidogrel. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Coronary Syndrome, Percutaneous Coronary Intervention
- What is being tested?
- Ticagrelor, Prasugrel, Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 2 sitesCanada
- Study dates
- Sep 2014to Jun 2017
- Phase
- Phase 2/3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients: age >18 yrs, < 75yrs
- -> 60 kg ( since March 2015 age >75 and < 60 kg eligible - but prasugrel reduced to 5mg daily if randomized to personalized therapy arm)
- NSTEMI undergoing PCI will be eligible
Who cannot join
- Patients will be excluded if they have: i) a contra-indication for clopidogrel or prasugrel or ticagrelor (as per monograph), ii) have an intolerance to aspirin, iii) have absolute requirement for ticagrelor or prasugrel (e.g. stent thrombosis, allergic reaction to clopidogrel), iv) requirement for anti-coagulation treatment, v) a history of stroke, TIA or intracranial hemorrhage , vi) a platelet count < 100,000/μl, vii) a known bleeding diathesis, viii) hematocrit <30% or >52%, ix) severe liver dysfunction, x) renal insufficiency (creatinine clearance < 30ml/min), xi) adjuvant therapy with a glycoprotein IIbIIIa inhibitor.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Montreal Heart Institute
Montreal, Quebec, H1T1C8
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y4W7
About this study
Official title: Reassessment of Anti-Platelet Therapy Using InDividualized Strategies - Modifying Acute CoroNary Syndrome Algorithms Based on Genetic and Demographic Evaluation: The RAPID-MANAGE Study
In patients with heart attacks, the treatment of choice is to restore blood flow with percutaneous coronary intervention (PCI) (use of stents (metal meshes) to open blockages). After PCI, the standard drug treatment includes aspirin and clopidogrel. These medications block full function of the platelet cells, which are responsible for clotting. Despite their use, patients after PCI are at risk for heart attacks, sudden clotting of stents or death. A major contributor may be resistance to clopidogrel. New more potent drugs, which can overcome the resistance, are now available; however, they come with an increase chance of severe bleeding and costs. An ideal solution would be to identify at-risk patients and selectively treat them with more potent drugs, while lower-risk patients continue with clopidogrel. This type of strategy (personalized strategy) would decrease heart attacks and death (compared to clopidogrel), while also preventing bleeding complications (compared to treating all patients with the new drugs).
Of resistant patients, many carry genes (inherited units) that prevent proper absorption of clopidogrel. Our group has developed and tested a new bedside genetic test, which identifies carriers of at-risk genes. However, this technique alone does not identify all at-risk patients. Consequently, we have now devised a novel tool, which combines genetics with patient characteristics to identify high-risk patients.
The present study combines this new tool into a strategy for personalized treatment. Patients with heart attacks who undergo PCI will be randomly assigned to 1 of 3 strategies: a) new personalized strategy, b) clopidogrel strategy (previous standard drug) or c) ticagrelor strategy (stronger approved drug). The function of the platelet cells will be measured at 1 month to determine potential benefits. Evaluation of this new personalized strategy is important for improving patient outcomes after PCI. The hypothesis is that patients receiving a personalized strategy will have decrease risk for future heart attacks and bleeding.
- Being tested
- Ticagrelor, Prasugrel, Clopidogrel
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor, Prasugrel, ClopidogrelDrug
| Study group | Role | What they receive |
|---|---|---|
| Personalized Therapy | Experimental | A point-of-care bedside genetic test for CYP2C19*2 and CYP2C19*3 using a buccal swab will be conducted.2 P2Y12 inhibitory drug therapy will be then be directed based on a risk algorithm (integrating genotyping and clinical variables). Patients with "high ischemic risk" are defined as having (*2 or *3) and/or diabetes and/or (having age>65 AND BMI>=28). "High-risk" patients will be switched to prasugrel at 10mg daily, while "low ischemic risk" patients be kept on clopidogrel 75 daily. For patients >age 75 or wt < 60 kg, prasugrel will be reduced to 5mg daily. Receives: Drug: Ticagrelor, Prasugrel, Clopidogrel |
| Ticagrelor | Active comparator | Patients will be treated with a 90mg twice daily regimen of Ticagrelor Receives: Drug: Ticagrelor, Prasugrel, Clopidogrel |
| Clopidogrel registry arm | Other | A concurrent registry of patients (not randomized) who are receiving clopidogrel only (as decided by treating physician) will be followed as a comparator group. Receives: Drug: Ticagrelor, Prasugrel, Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients in Therapeutic Window
The primary endpoint is the proportion of patients outside of the "therapeutic window" in the personalized therapy (PN) arm compared to the ticagrelor (TG) arm at 1 month. The "therapeutic window" will be defined by platelet function values (VerifyNow P2Y12 assay - P2Y12 reaction unit (PRU) ≤ 208 (correlated with decreased ischemic outcomes) AND PRU >= 85 (correlated with decrease bleeding). This is a surrogate of NACE (net adverse clinical events)
Measured: 1 month
Secondary outcomes (4)
P2Y12 Reaction Unit (PRU)
change in PRU from baseline, day 1 to 1 month in each of the groups
Measured: Baseline, Day 1, 1 month
Bleeding
the incidence of bleeding (defined by TIMI minor and major bleeds) among groups
Measured: 1 month, 6 months
MACE
combined clinical endpoint (MACE) including death, myocardial infarction(MI) or urgent target vessel revascularization (TVR)
Measured: 1 month, 6 months
Stent thrombosis
stent thrombosis (ARC definite/probable)
Measured: 1 month, 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startSep 2014
- Primary completionOct 2016
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- More trials run by Ottawa Heart Institute Research CorporationThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Derek So, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02044146
- Sponsor's protocol ID
- 20130601
- Acronym
- RAPID MANAGE
- Status last verified
- Oct 2018
- First submitted
- 21 Jan 2014
- Last updated
- 5 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reassessment of Anti-Platelet Therapy Using InDividualized Strategies - Modifying Acute CoroNary Syndrome Algorithms Based on Genetic and Demographic Evaluation: The RAPID-MANAGE Study
- ClinicalTrials.gov ID
- NCT02044146
- Acronym / sponsor ID
- RAPID MANAGE / 20130601
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Sep 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 23 Jan 2014 (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.
In patients with heart attacks, the treatment of choice is to restore blood flow with percutaneous coronary intervention (PCI) (use of stents (metal meshes) to open blockages). After PCI, the standard drug treatment includes aspirin and clopidogrel. These medications block full function of the platelet cells, which are responsible for clotting. Despite their use, patients after PCI are at risk for heart attacks, sudden clotting of stents or death. A major contributor may be resistance to clopidogrel. New more potent drugs, which can overcome the resistance, are now available; however, they come with an increase chance of severe bleeding and costs. An ideal solution would be to identify at-risk patients and selectively treat them with more potent drugs, while lower-risk patients continue with clopidogrel. This type of strategy (personalized strategy) would decrease heart attacks and death (compared to clopidogrel), while also preventing bleeding complications (compared to treating all patients with the new drugs).
Of resistant patients, many carry genes (inherited units) that prevent proper absorption of clopidogrel. Our group has developed and tested a new bedside genetic test, which identifies carriers of at-risk genes. However, this technique alone does not identify all at-risk patients. Consequently, we have now devised a novel tool, which combines genetics with patient characteristics to identify high-risk patients.
The present study combines this new tool into a strategy for personalized treatment. Patients with heart attacks who undergo PCI will be randomly assigned to 1 of 3 strategies: a) new personalized strategy, b) clopidogrel strategy (previous standard drug) or c) ticagrelor strategy (stronger approved drug). The function of the platelet cells will be measured at 1 month to determine potential benefits. Evaluation of this new personalized strategy is important for improving patient outcomes after PCI. The hypothesis is that patients receiving a personalized strategy will have decrease risk for future heart attacks and bleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Personalized Therapy | Experimental | Drug: Ticagrelor, Prasugrel, ClopidogrelA point-of-care bedside genetic test for CYP2C19*2 and CYP2C19*3 using a buccal swab will be conducted.2 P2Y12 inhibitory drug therapy will be then be directed based on a risk algorithm (integrating genotyping and clinical variables). Patients with "high ischemic risk" are defined as having (*2 or *3) and/or diabetes and/or (having age>65 AND BMI>=28). "High-risk" patients will be switched to prasugrel at 10mg daily, while "low ischemic risk" patients be kept on clopidogrel 75 daily. For patients >age 75 or wt < 60 kg, prasugrel will be reduced to 5mg daily. |
| Ticagrelor | Active comparator | Drug: Ticagrelor, Prasugrel, ClopidogrelPatients will be treated with a 90mg twice daily regimen of Ticagrelor |
| Clopidogrel registry arm | Other | Drug: Ticagrelor, Prasugrel, ClopidogrelA concurrent registry of patients (not randomized) who are receiving clopidogrel only (as decided by treating physician) will be followed as a comparator group. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients: age >18 yrs, < 75yrs
- -> 60 kg ( since March 2015 age >75 and < 60 kg eligible - but prasugrel reduced to 5mg daily if randomized to personalized therapy arm)
- NSTEMI undergoing PCI will be eligible
Key exclusion criteria (1 listed)
- Patients will be excluded if they have: i) a contra-indication for clopidogrel or prasugrel or ticagrelor (as per monograph), ii) have an intolerance to aspirin, iii) have absolute requirement for ticagrelor or prasugrel (e.g. stent thrombosis, allergic reaction to clopidogrel), iv) requirement for anti-coagulation treatment, v) a history of stroke, TIA or intracranial hemorrhage , vi) a platelet count < 100,000/μl, vii) a known bleeding diathesis, viii) hematocrit <30% or >52%, ix) severe liver dysfunction, x) renal insufficiency (creatinine clearance < 30ml/min), xi) adjuvant therapy with a glycoprotein IIbIIIa inhibitor.
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 |
|---|---|---|
| Ticagrelor, Prasugrel, Clopidogrel | Drug | Clopidogrel registry arm, Personalized Therapy, Ticagrelor |
Primary outcome
Proportion of Patients in Therapeutic Window
Time frame: 1 month
The primary endpoint is the proportion of patients outside of the "therapeutic window" in the personalized therapy (PN) arm compared to the ticagrelor (TG) arm at 1 month. The "therapeutic window" will be defined by platelet function values (VerifyNow P2Y12 assay - P2Y12 reaction unit (PRU) ≤ 208 (correlated with decreased ischemic outcomes) AND PRU >= 85 (correlated with decrease bleeding). This is a surrogate of NACE (net adverse clinical events)
4 secondary outcomes
P2Y12 Reaction Unit (PRU)
Time frame: Baseline, Day 1, 1 month
Bleeding
Time frame: 1 month, 6 months
MACE
Time frame: 1 month, 6 months
Stent thrombosis
Time frame: 1 month, 6 month
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 5 Oct 2018.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ticagrelor, Prasugrel, Clopidogrel in people with Acute Coronary Syndrome and Percutaneous Coronary Intervention, run by Ottawa Heart Institute Research Corporation at 2 sites in Canada.
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 1 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 5 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Proportion of Patients in Therapeutic Window (time frame: 1 month). 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 5 Oct 2018.