Diabetes Mellitus, Type 2Phase 4OPTIMUS-6NCT03437044
Low Maintenance Dose Ticagrelor Versus Clopidogrel in Diabetes Patients Undergoing PCI
A Phase 4 study testing Ticagrelor and Clopidogrel in people with Diabetes Mellitus, Type 2 and Coronary Artery Disease, run by University of Florida at 1 site in United States.
Trial summary
To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in patients with DM who are known to have impaired response to clopidogrel therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2, Coronary Artery Disease
- What is being tested?
- Ticagrelor and Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Mar 2018to 27 Jun 2020
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Men or women ≥18 years of age
- Diagnosed with type 2 DM defined by ongoing glucose lowering drug (oral medications and / or insulin) treatment for at least 1 month
- Presence of CAD undergoing elective PCI* * Patients will need to be cardiac enzyme-negative prior to undergoing coronary angiography. Patient will need to be on a background of aspirin therapy (treated with a 325 mg LD prior to coronary angiography unless already on chronic low-dose aspirin therapy). Patients on maintenance clopidogrel 75 mg therapy for at least 1 week due to a prior vascular intervention will also be eligible. However, patients on clopidogrel, ticagrelor or prasugrel due to a prior acute major cardiovascular event (MI or stroke) will not be eligible.
Who cannot join
- Previous MI (with the exception of definite non-type 1 MI [eg, due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia])
- Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)
- Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
- On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)
- Planned use of aspirin treatment at doses >100 mg od
- Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot be stopped for the course of the study:
Show all 23Show fewer
- Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir
- CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily
- Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
- Patients with known bleeding diathesis or coagulation disorder
- History of previous intracerebral bleed at any time, gastrointestinal (GI) bleed within the past 6 months prior to randomization, or major surgery within 30 days prior to randomization
- Active pathological bleeding
- Hypersensitivity to ticagrelor and clopidogrel or any of the excipients
- Increased risk of bradycardic events (eg, known sick sinus syndrome, second or third degree AV block or previous documented syncope suspected to be due to bradycardia) unless treated with a pacemaker
- Known severe liver disease (eg, ascites and/or clinical signs of coagulopathy)
- Renal failure requiring dialysis
- Known platelet count <80x106/mL
- Known hemoglobin <9 g/dL
- Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopause) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding. If a subject becomes pregnant during the course of the study the investigational product should be discontinued immediately [the outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth or congenital abnormality) will be followed up and documented even if the subject was discontinued from the study].
- Inability of the patient to understand and/or comply with study procedures and/or follow up, in the opinion of the investigator, OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
- Life expectancy of less than 1 month based on investigator's judgement
- Participation in another clinical study with an investigational (defined as non-FDA approved) product within 28 days prior to enrolment
- Previous randomization in the present study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Comparison of Platelet Inhibition Using a Low Maintenance Dose Ticagrelor Regimen Versus Standard Dose Clopidogrel in Diabetes Mellitus Patients Without Prior Major Cardiovascular Events Undergoing Elective Percutaneous Coronary Intervention: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-6 Study
To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in patients with DM who are known to have impaired response to clopidogrel therapy. Since DM patients frequently require elective PCI due to chronic progression of CAD (and not solely because of an acute thrombotic complication), and clopidogrel remains the guideline recommended P2Y12 inhibiting therapy for these patients, understanding the PD effects of the ticagrelor 60 mg bid regimen in this setting is an unmet clinical need. This is also in light of the ongoing THEMIS trial which is specifically evaluating the impact of the ticagrelor 60 mg bid dosing regimen in type 2 DM patients without a prior major CV event.
Read the detailed description
Patients with diabetes mellitus (DM) are characterized by platelet hyperreactivity and reduced pharmacodynamic (PD) effects to several oral antiplatelet agents, including clopidogrel. In addition to the hyperreactive platelet phenotype, impaired drug metabolism as well as increased platelet turnover rates may contributed to impaired clopidogrel-induced antiplatelet effects in DM patients. These observations may contribute to the higher ischemic event rates, including stent thrombosis, observed in DM patients compared with non-DM patients treated with clopidogrel.
Ticagrelor is characterized by more prompt, potent and predictable antiplatelet effects compared with clopidogrel and lower ischemic events in patients with an acute coronary syndrome (ACS) on a background of aspirin therapy. In patients who experienced a prior (1-3 years) myocardial infarction (MI), compared with placebo, ticagrelor 60 mg bid on a background of aspirin therapy also reduced long-term ischemic events, with a mortality benefit observed in DM patients.
To date the PD effects of ticagrelor versus clopidogrel in DM largely derive from post-hoc assessments or in stabilized patients (e.g. >30 days after PCI), and have not been prospectively evaluated in the context of elective PCI procedures. Moreover, PD studies with the ticagrelor 60 mg bid regimen are limited. Therefore, the aim of this investigation will be to compare the PD effects of a ticagrelor 60 mg bid versus clopidogrel 75 mg od MD regimen in DM patients without a prior major CV event undergoing elective PCI.
- Conditions
- Diabetes Mellitus, Type 2, Coronary Artery Disease
- Being tested
- Ticagrelor, Clopidogrel
- Keywords
- diabetes mellitus, percutaneous coronary intervention, ticagrelor, clopidogrel, coronary artery disease
- Medical subject headings
- Diabetes Mellitus, Type 2, Coronary Artery Disease, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called Brilinta
After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.
ClopidogrelDrug
Also called Plavix
After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor | Experimental | 180 mg loading dose (LD) followed by a 60 mg bid maintenance (MD) starting 12 h (± 1 h) after the LD Receives: Drug: Ticagrelor |
| Clopidogrel | Active comparator | 600 mg LD followed by a 75 mg od MD starting 24 hours (± 1 h) after the LD Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
P2Y12 Reaction Units (PRU)
The primary endpoint of our study will be platelet reactivity, measured as PRU level using VerifyNow PRU, of ticagrelor versus clopidogrel MD at 30 days after PCI, immediately pre-dosing dosing (trough levels). PRU is a marker of platelet reactivity. Higher PRU values correspond to higher aggregation and lower response to antiplatelet therapy.
Measured: 30 days
Secondary outcomes (1)
Platelet Reactivity Index (PRI)
Platelet reactivity measured as PRI% using whole blood vasodilator-stimulated phosphoprotein (VASP), of ticagrelor versus clopidogrel MD at 30 days after PCI, immediately pre-dosing dosing (trough levels). PRI% is a marker of platelet reactivity. Higher PRI values correspond to higher aggregation and lower response to antiplatelet therapy.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start14 Mar 2018
- Primary completion27 Jun 2019
- Study completion27 Jun 2020
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 Mellitus, Type 2Studies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Dominick J Angiolillo, MD,PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437044
- Sponsor's protocol ID
- ESR 13396
- Acronym
- OPTIMUS-6
- Status last verified
- Nov 2021
- First submitted
- 12 Feb 2018
- Last updated
- 30 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ortega-Paz L, Thomas CD, Laudani C, Giordano S, Franchi F, Tunehag KR, Rollini F, Durukan S, Rossi JS, Farahmandsadr M, Stouffer GA, Been L, Keeley EC, Duarte JD, Beitelshees AL, Lee CR, Cavallari LH, Angiolillo DJ. Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants. Clin Pharmacol Ther. 2026 Jan;119(1):168-178. doi: 10.1002/cpt.70045. Epub 2025 Aug 28.
PubMed 40875095
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparison of Platelet Inhibition Using a Low Maintenance Dose Ticagrelor Regimen Versus Standard Dose Clopidogrel in Diabetes Mellitus Patients Without Prior Major Cardiovascular Events Undergoing Elective Percutaneous Coronary Intervention: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-6 Study
- ClinicalTrials.gov ID
- NCT03437044
- Acronym / sponsor ID
- OPTIMUS-6 / ESR 13396
- Conditions
- Diabetes Mellitus, Type 2, Coronary Artery Disease
- Keywords
- diabetes mellitus, percutaneous coronary intervention, ticagrelor, clopidogrel, coronary artery disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 14 Mar 2018 (actual)
- Primary completion
- 27 Jun 2019 (actual)
- Study completion
- 27 Jun 2020 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Posted 5 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in patients with DM who are known to have impaired response to clopidogrel therapy. Since DM patients frequently require elective PCI due to chronic progression of CAD (and not solely because of an acute thrombotic complication), and clopidogrel remains the guideline recommended P2Y12 inhibiting therapy for these patients, understanding the PD effects of the ticagrelor 60 mg bid regimen in this setting is an unmet clinical need. This is also in light of the ongoing THEMIS trial which is specifically evaluating the impact of the ticagrelor 60 mg bid dosing regimen in type 2 DM patients without a prior major CV event.
Detailed description
Patients with diabetes mellitus (DM) are characterized by platelet hyperreactivity and reduced pharmacodynamic (PD) effects to several oral antiplatelet agents, including clopidogrel. In addition to the hyperreactive platelet phenotype, impaired drug metabolism as well as increased platelet turnover rates may contributed to impaired clopidogrel-induced antiplatelet effects in DM patients. These observations may contribute to the higher ischemic event rates, including stent thrombosis, observed in DM patients compared with non-DM patients treated with clopidogrel.
Ticagrelor is characterized by more prompt, potent and predictable antiplatelet effects compared with clopidogrel and lower ischemic events in patients with an acute coronary syndrome (ACS) on a background of aspirin therapy. In patients who experienced a prior (1-3 years) myocardial infarction (MI), compared with placebo, ticagrelor 60 mg bid on a background of aspirin therapy also reduced long-term ischemic events, with a mortality benefit observed in DM patients.
To date the PD effects of ticagrelor versus clopidogrel in DM largely derive from post-hoc assessments or in stabilized patients (e.g. >30 days after PCI), and have not been prospectively evaluated in the context of elective PCI procedures. Moreover, PD studies with the ticagrelor 60 mg bid regimen are limited. Therefore, the aim of this investigation will be to compare the PD effects of a ticagrelor 60 mg bid versus clopidogrel 75 mg od MD regimen in DM patients without a prior major CV event undergoing elective PCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective randomized
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor | Experimental | Drug: Ticagrelor180 mg loading dose (LD) followed by a 60 mg bid maintenance (MD) starting 12 h (± 1 h) after the LD |
| Clopidogrel | Active comparator | Drug: Clopidogrel600 mg LD followed by a 75 mg od MD starting 24 hours (± 1 h) after the LD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of informed consent prior to any study specific procedures
- Men or women ≥18 years of age
- Diagnosed with type 2 DM defined by ongoing glucose lowering drug (oral medications and / or insulin) treatment for at least 1 month
- Presence of CAD undergoing elective PCI* * Patients will need to be cardiac enzyme-negative prior to undergoing coronary angiography. Patient will need to be on a background of aspirin therapy (treated with a 325 mg LD prior to coronary angiography unless already on chronic low-dose aspirin therapy). Patients on maintenance clopidogrel 75 mg therapy for at least 1 week due to a prior vascular intervention will also be eligible. However, patients on clopidogrel, ticagrelor or prasugrel due to a prior acute major cardiovascular event (MI or stroke) will not be eligible.
Key exclusion criteria (23 listed)
- Previous MI (with the exception of definite non-type 1 MI [eg, due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia])
- Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)
- Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
- On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)
- Planned use of aspirin treatment at doses >100 mg od
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: BrilintaAfter providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days. | Drug | Ticagrelor |
| ClopidogrelAlso: PlavixAfter providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days. | Drug | Clopidogrel |
Primary outcome
P2Y12 Reaction Units (PRU)
Time frame: 30 days
The primary endpoint of our study will be platelet reactivity, measured as PRU level using VerifyNow PRU, of ticagrelor versus clopidogrel MD at 30 days after PCI, immediately pre-dosing dosing (trough levels). PRU is a marker of platelet reactivity. Higher PRU values correspond to higher aggregation and lower response to antiplatelet therapy.
1 secondary outcome
Platelet Reactivity Index (PRI)
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40875095Ortega-Paz L, Thomas CD, Laudani C, Giordano S, Franchi F, Tunehag KR, Rollini F, Durukan S, Rossi JS, Farahmandsadr M, Stouffer GA, Been L, Keeley EC, Duarte JD, Beitelshees AL, Lee CR, Cavallari LH, Angiolillo DJ. Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants. Clin Pharmacol Ther. 2026 Jan;119(1):168-178. doi: 10.1002/cpt.70045. Epub 2025 Aug 28.
- 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 J 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 Phase 4 study testing Ticagrelor and Clopidogrel in people with Diabetes Mellitus, Type 2 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 23 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 30 Nov 2021. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2021). 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 (PRU) (time frame: 30 days). 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 NCT03437044, 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 30 Nov 2021.