Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes

NCT01852214 | Completed Results DMC

• 1 other identifier: UFJ 2011-184
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Diabetes Mellitus; Coronary Artery Disease

Keywords

Diabetes mellitus; Coronary artery disease; prasugrel; ticagrelor

Outcome Measures

Primary Outcomes (1)

• 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.

  1 week

Secondary Outcomes (3)

• P2Y12 Reaction Units

  2 hours

• Platelet Reactivity Index

  1 week

• Platelet Reactivity Index

  2 hours

Study Arms (2)

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.

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.

Drug: Prasugrel; Drug: Ticagrelor

Interventions

Prasugrel DRUG

Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose

Also known as: Effient

Prasugrel first, then ticagrelor; Ticagrelor first, then prasugrel

Ticagrelor DRUG

Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose

Also known as: Brillinta

Prasugrel first, then ticagrelor; Ticagrelor first, then prasugrel

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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\*.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• 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.

  PMID: 27559041 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dominick J. Angiolillo, MD, PhD
• Organization: University of Florida College of Medicine-Jacksonville

dominick.angiolillo@jax.ufl.edu

+1-904-244-3933

Study Officials

• Dominick Angiolillo, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 17, 2016
• Results First Posted: October 17, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)