An interventional study of Prasugrel and Ticagrelor in Diabetes Mellitus and Coronary Artery Disease, sponsored by University of Florida. Completed at 1 site in United States. Open to participants aged 18 Years to 74 Years. Per ClinicalTrials.gov, last updated 2016-10-17.
Sponsored by University of Florida · Not applicable, Interventional, and Treatment
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.
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.
5,598 studies on the registry are indexed under Coronary Artery Disease; 957 are open to participants now.
This study's enrollment of 50 is below the median of 124 across 3,436 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →University of Florida is the lead sponsor of 1,254 studies on the registry; 201 are open to participants now.
Of its 170 completed or terminated interventional studies of FDA-regulated products, 136 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Pregnant females*.
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.
Drug: Prasugrel · Drug: Ticagrelor
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.
Drug: Prasugrel · Drug: Ticagrelor
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
Also known as: Effient
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Also known as: Brillinta
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.
Time frame: 1 week
P2Y12 Reaction Units
Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
Time frame: 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.
Time frame: 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.
Time frame: 2 hours
Between February 2013 and July 2015, a total of 61 subjects agreed to participate in the study; 11 subjects were excluded and thus a total of 50 subjects were randomized (prasugrel first n=26; ticagrelor first n=24).
| Milestone | Prasugrel First, Then Ticagrelor | Ticagrelor First, Then Prasugrel |
|---|---|---|
| Started | 26 | 24 |
| Completed | 25 | 21 |
| Not completed | 1 | 3 |
| Withdrew: Adverse event | 1 | 2 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Prasugrel First, Then Ticagrelor | Ticagrelor First, Then Prasugrel |
|---|---|---|
| Started | 25 | 21 |
| Completed | 25 | 20 |
| Not completed | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Prasugrel First, Then Ticagrelor | Ticagrelor First, Then Prasugrel |
|---|---|---|
| Started | 25 | 20 |
| Completed | 25 | 20 |
| Not completed | 0 | 0 |
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.
| PRU | Prasugrel | Ticagrelor |
|---|---|---|
| P2Y12 Reaction Units | 83 (63 to 103) | 52 (32 to 72) |
Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
| PRU | Prasugrel | Ticagrelor |
|---|---|---|
| P2Y12 Reaction Units | 97 (78 to 117) | 75 (56 to 95) |
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.
| PRI | Prasugrel | Ticagrelor |
|---|---|---|
| Platelet Reactivity Index | 36 (30 to 41) | 36 (30 to 42) |
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.
| PRI | Prasugrel | Ticagrelor |
|---|---|---|
| Platelet Reactivity Index | 35 (25 to 45) | 37 (29 to 46) |
Collected over Through study completion, up to 46 days.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Safety Population: Patients Receiving Prasugrel | — | 0/46 (0%) | 4/46 (8.7%) |
| Safety Population: Patients Receiving Ticagrelor | — | 0/49 (0%) | 10/49 (20.4%) |
| Event | Safety Population: Patients Receiving Prasugrel | Safety Population: Patients Receiving Ticagrelor |
|---|---|---|
| DyspneaRespiratory, thoracic and mediastinal disorders | 3/46 | 9/49 |
| BARC type 1 bleedingBlood and lymphatic system disorders | 1/46 | 1/49 |
All analyses of platelet function were conducted on the pharmacodynamic population, which was defined as all randomized subjects who received study drug, successfully completed at least one treatment period of the study and had valid data for the primary end point (n=46)
| Age, Continuous(years) | Overall Population |
|---|---|
| Mean | 59 ± 8 |
| Sex: Female, Male(Participants) | Overall Population |
|---|---|
| Female | 13 |
| Male | 33 |
| Race (NIH/OMB)(Participants) | Overall Population |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 16 |
| White | 30 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Type of diabetes(participants) | Overall Population |
|---|---|
| Insulin-dependent | 26 |
| Non-insulin-dependent | 20 |
Plan to share: No
This study is completed, as verified in Jun 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Florida