Diabetes MellitusNCT01852214
Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes
A study testing Prasugrel and Ticagrelor in people with Diabetes Mellitus and Coronary Artery Disease, run by University of Florida at 1 site in United States.
Trial summary
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Diabetes Mellitus, Coronary Artery Disease
- What is being tested?
- Prasugrel and Ticagrelor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Aug 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with known (angiographically documented) CAD.
- On maintenance treatment with aspirin (81 mg per day) for at least 1-month as per standard of care.
- Type 2 DM on treatment with oral hypoglycemic agents and/or insulin.
- Age between 18 and 74 years old.
Who cannot join
- History of stroke, transient ischemic attack or intracranial bleeding.
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor).
- Known allergies to aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor.
- Weight <60kg.
- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran).
- Blood dyscrasia or bleeding diathesis.
Show all 16Show fewer
- Platelet count <80x106/mL.
- Hemoglobin <10 g/dL.
- Active bleeding or hemodynamic instability.
- Creatinine Clearance <30 mL/minute.
- Baseline ALT >2.5 times the upper limit of normal.
- Hb A1c ≥ 10 mg/dL within 3 months.
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
- Drugs interfering CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- Pregnant females*.
- Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacodynamic Comparison of Prasugrel vs. Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Head-to-head comparisons between the two drugs are lacking.
Read the detailed description
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Upregulation of platelet P2Y12 receptor mediated signaling has been shown in DM patients and may contribute to these pharmacodynamic observations, suggesting the need for more potent P2Y12 inhibiting strategies in these patients. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Therefore, prasugrel and ticagrelor represent attractive treatment options for patients with DM. This is also supported by the DM sub-group analysis of the pivotal TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction) and PLATO (Platelet Inhibition and Patient Outcomes) trials, which have led to approval of prasugrel and ticagrelor, respectively. Although results of these sub-group analysis suggest that prasugrel is associated with an enhanced benefit in DM patients, while ticagrelor effects in DM patients are consistent with the overall study population, only head-to-head comparisons between the two drugs can elucidate if these exert differential effects on platelets from DM patients. However, the pharmacodynamic studies comparing prasugrel with ticagrelor in DM patients are lacking. The ever growing DM population at high risk of recurrent atherothrombotic events underscores the need to define antiplatelet treatment strategies leading to more optimal platelet inhibition in these patients.
- Conditions
- Diabetes Mellitus, Coronary Artery Disease
- Being tested
- Prasugrel, Ticagrelor
- Keywords
- Diabetes mellitus, Coronary artery disease, prasugrel, ticagrelor
- Medical subject headings
- Diabetes Mellitus, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrasugrelDrug
Also called Effient
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
TicagrelorDrug
Also called Brillinta
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
| Study group | Role | What they receive |
|---|---|---|
| Prasugrel first, then ticagrelor | Active comparator | Patients randomized to prasugrel will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (ticagrelor), which will be administered for 1-week. Receives: Drug: Prasugrel; Drug: Ticagrelor |
| Ticagrelor first, then prasugrel | Active comparator | Patients randomized to ticagrelor will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (prasugrel), which will be administered for 1-week. Receives: Drug: Prasugrel; Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
P2Y12 Reaction Units
The primary endpoint is the comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel). Treatment effects were evaluated comparing PRU observed in the overall patient population after prasugrel treatment with those achieved after ticagrelor regardless of the sequence.
Measured: 1 week
Secondary outcomes (3)
P2Y12 Reaction Units
Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
Measured: 2 hours
Platelet Reactivity Index
The comparison of the platelet reactivity index (PRI) values determined by vasodilator-stimulated phosphoprotein (VASP) between both treatments (ticagrelor or prasugrel). VASP was measured by quantitative flow cytometry using commercially available labelled monoclonal antibodies. A low PRI is indicative of high platelet inhibition.
Measured: 1 week
Platelet Reactivity Index
The comparison of the platelet reactivity index (PRI) values determined by vasodilator-stimulated phosphoprotein (VASP) between both treatments (ticagrelor or prasugrel). VASP was measured by quantitative flow cytometry using commercially available labelled monoclonal antibodies. A low PRI is indicative of high platelet inhibition.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2013 (estimated)
- Study startFeb 2013
- Primary completionJul 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominick Angiolillo, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01852214
- Sponsor's protocol ID
- UFJ 2011-184
- Status last verified
- Jun 2016
- First submitted
- 8 May 2013
- Last updated
- 17 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, Duarte VE, Cho JR, Been L, Zenni MM, Bass TA, Angiolillo DJ. Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation. 2016 Sep 13;134(11):780-92. doi: 10.1161/CIRCULATIONAHA.116.023402. Epub 2016 Aug 24.
PubMed 27559041
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacodynamic Comparison of Prasugrel vs. Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT01852214
- Acronym / sponsor ID
- UFJ 2011-184
- Conditions
- Diabetes Mellitus, Coronary Artery Disease
- Keywords
- Diabetes mellitus, Coronary artery disease, prasugrel, ticagrelor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 13 May 2013 (estimated)
- Results
- Posted 17 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Head-to-head comparisons between the two drugs are lacking.
Detailed description
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Upregulation of platelet P2Y12 receptor mediated signaling has been shown in DM patients and may contribute to these pharmacodynamic observations, suggesting the need for more potent P2Y12 inhibiting strategies in these patients. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Therefore, prasugrel and ticagrelor represent attractive treatment options for patients with DM. This is also supported by the DM sub-group analysis of the pivotal TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction) and PLATO (Platelet Inhibition and Patient Outcomes) trials, which have led to approval of prasugrel and ticagrelor, respectively. Although results of these sub-group analysis suggest that prasugrel is associated with an enhanced benefit in DM patients, while ticagrelor effects in DM patients are consistent with the overall study population, only head-to-head comparisons between the two drugs can elucidate if these exert differential effects on platelets from DM patients. However, the pharmacodynamic studies comparing prasugrel with ticagrelor in DM patients are lacking. The ever growing DM population at high risk of recurrent atherothrombotic events underscores the need to define antiplatelet treatment strategies leading to more optimal platelet inhibition in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prasugrel first, then ticagrelor | Active comparator | Drug: Prasugrel, Drug: TicagrelorPatients randomized to prasugrel will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (ticagrelor), which will be administered for 1-week. |
| Ticagrelor first, then prasugrel | Active comparator | Drug: Prasugrel, Drug: TicagrelorPatients randomized to ticagrelor will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (prasugrel), which will be administered for 1-week. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with known (angiographically documented) CAD.
- On maintenance treatment with aspirin (81 mg per day) for at least 1-month as per standard of care.
- Type 2 DM on treatment with oral hypoglycemic agents and/or insulin.
- Age between 18 and 74 years old.
Key exclusion criteria (16 listed)
- History of stroke, transient ischemic attack or intracranial bleeding.
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor).
- Known allergies to aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor.
- Weight <60kg.
- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran).
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 |
|---|---|---|
| PrasugrelAlso: EffientPatients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose | Drug | Prasugrel first, then ticagrelor, Ticagrelor first, then prasugrel |
| TicagrelorAlso: BrillintaPatients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose | Drug | Prasugrel first, then ticagrelor, Ticagrelor first, then prasugrel |
Primary outcome
P2Y12 Reaction Units
Time frame: 1 week
The primary endpoint is the comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel). Treatment effects were evaluated comparing PRU observed in the overall patient population after prasugrel treatment with those achieved after ticagrelor regardless of the sequence.
3 secondary outcomes
P2Y12 Reaction Units
Time frame: 2 hours
Platelet Reactivity Index
Time frame: 1 week
Platelet Reactivity Index
Time frame: 2 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27559041Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, Duarte VE, Cho JR, Been L, Zenni MM, Bass TA, Angiolillo DJ. Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation. 2016 Sep 13;134(11):780-92. doi: 10.1161/CIRCULATIONAHA.116.023402. Epub 2016 Aug 24.
- 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.
Dominick Angiolillo, MD, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prasugrel and Ticagrelor in people with Diabetes Mellitus and Coronary Artery Disease, run by University of Florida at 1 site in United States.
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 4 inclusion and 16 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 17 Oct 2016. 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 States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
P2Y12 Reaction Units (time frame: 1 week). 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 NCT01852214, 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 17 Oct 2016.