High Ticagrelor Loading Dose in STEMI

NCT01898442 | Completed Phase 2 Results DMC

• 1 other identifier: TicagSTEMI
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.

Conditions

Coronary Artery Disease

Keywords

platelet function; ticagrelor; STEMI

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity by VerifyNow P2Y12

  The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration

  1 hour

Secondary Outcomes (5)

• Platelet Reactivity by VerifyNow P2Y12 at Other Time Points

  30 min and 2, 4, 8, 24 hours

• Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points

  30 min and 1, 2, 4, 8, 24 hours

• Pharmacokinetic Profiles of Ticagrelor (Tmax)

  24 hours

• Pharmacokinetic Profiles of Ticagrelor (Cmax)

  24 hours

• Pharmacokinetic Profiles of Ticagrelor (AUC0-t)

  24 hours

Study Arms (3)

Ticagrelor 180

ACTIVE COMPARATOR

Standard ticagrelor 180mg loading dose

Drug: Ticagrelor 180mg

Ticagrelor 270mg

EXPERIMENTAL

High ticagrelor 270mg loading dose

Drug: Ticagrelor 270mg

Ticagrelor 360mg

EXPERIMENTAL

High ticagrelor 360mg loading dose

Drug: Ticagrelor 360mg

Interventions

Ticagrelor 180mg DRUG

Rndomization to standard or high ticagrelor loading dose regimens

Also known as: Brilinta

Ticagrelor 180

Ticagrelor 270mg DRUG

Randomization to standard or high loading dose regimen

Also known as: Brilinta

Ticagrelor 270mg

Ticagrelor 360mg DRUG

Randomization to standrad or high loading dose regimen

Also known as: Brilinta

Ticagrelor 360mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with ST-elevation myocardial infarction undergoing primary PCI.
• Age between 18 and 80 years old.

You may not qualify if:

• History of prior intracranial bleeding.
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.
• Known allergies to aspirin or ticagrelor.
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
• Treatment with IIb/IIIa glycoprotein inhibitors.
• Fibrinolytics within 24 hours
• Known blood dyscrasia or bleeding diathesis.
• Known platelet count \<80x106/mL.
• Known hemoglobin \<10 g/dL.
• Active bleeding.
• Hemodynamic instability.
• Known creatinine clearance \<30 mL/minute.
• Known severe hepatic dysfunction.
• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.

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, Cho JR, Bhatti M, DeGroat C, Ferrante E, Dunn EC, Nanavati A, Carraway E, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Impact of Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation. JACC Cardiovasc Interv. 2015 Sep;8(11):1457-1467. doi: 10.1016/j.jcin.2015.02.030.

  PMID: 26404199 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; ST Elevation Myocardial Infarction

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

The study was not powered to assess safety or efficacy, which would require larger clinical studies. Although laboratory personnel were blinded to treatment assignment, the study had an open-label design.

Results Point of Contact

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

dominick.angiolillo@jax.ufl.edu

9042443933

Study Officials

• Dominick Angiolillo, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2013
• First Posted: July 12, 2013
• Study Start: September 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 8, 2015
• Results First Posted: June 8, 2015

Record last verified: 2014-06

Locations

US (1)