Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Low Maintenance Dose Ticagrelor Versus Clopidogrel in Diabetes Patients Undergoing PCI (OPTIMUS-6)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03437044
Recruitment Status : Active, not recruiting
First Posted : February 19, 2018
Last Update Posted : April 30, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE February 12, 2018
First Posted Date  ICMJE February 19, 2018
Last Update Posted Date April 30, 2020
Actual Study Start Date  ICMJE March 14, 2018
Actual Primary Completion Date June 27, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
Platelet reactivity index (PRI) [ Time Frame: 30 days ]
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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Maintenance Dose Ticagrelor Versus Clopidogrel in Diabetes Patients Undergoing PCI
Official Title  ICMJE 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
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective randomized
Masking: None (Open Label)
Masking Description:
Staff performing PK/PD assessments will remain blinded to treatment assignment.
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes Mellitus, Type 2
  • Coronary Artery Disease
Intervention  ICMJE
  • Drug: Ticagrelor
    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.
    Other Name: Brilinta
  • Drug: Clopidogrel
    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.
    Other Name: Plavix
Study Arms  ICMJE
  • Experimental: Ticagrelor
    180 mg loading dose (LD) followed by a 60 mg bid maintenance (MD) starting 12 h (± 1 h) after the LD
    Intervention: Drug: Ticagrelor
  • Active Comparator: Clopidogrel
    600 mg LD followed by a 75 mg od MD starting 24 hours (± 1 h) after the LD
    Intervention: Drug: Clopidogrel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 13, 2019)
40
Original Estimated Enrollment  ICMJE
 (submitted: February 12, 2018)
42
Estimated Study Completion Date  ICMJE August 2020
Actual Primary Completion Date June 27, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Provision of informed consent prior to any study specific procedures
  2. Men or women ≥18 years of age
  3. Diagnosed with type 2 DM defined by ongoing glucose lowering drug (oral medications and / or insulin) treatment for at least 1 month
  4. 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.

Exclusion criteria:

  1. 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])
  2. Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)
  3. Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
  4. 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)
  5. Planned use of aspirin treatment at doses >100 mg od
  6. 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:

    • 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
  7. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
  8. Patients with known bleeding diathesis or coagulation disorder
  9. 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
  10. Active pathological bleeding
  11. Hypersensitivity to ticagrelor and clopidogrel or any of the excipients
  12. 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
  13. Known severe liver disease (eg, ascites and/or clinical signs of coagulopathy)
  14. Renal failure requiring dialysis
  15. Known platelet count <80x106/mL
  16. Known hemoglobin <9 g/dL
  17. 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].
  18. 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
  19. Life expectancy of less than 1 month based on investigator's judgement
  20. Participation in another clinical study with an investigational (defined as non-FDA approved) product within 28 days prior to enrolment
  21. Previous randomization in the present study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03437044
Other Study ID Numbers  ICMJE ESR 13396
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Dominick J Angiolillo, MD,PhD University of Florida
PRS Account University of Florida
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP