Effect of Prasugrel Versus Clopidogrel on Platelet Function After Bivalirudin Cessation

NCT01789814 | Completed Phase 4 Results

• 2 other identifiers: PraCloBiv2013CKTMCcardintervCK2013
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Early stent thrombosis has been noted with increased frequency in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) who are treated with bivalirudin and clopidogrel. The brief half life of bivalirudin acting in concert with the delayed action of clopidogrel likely exposes patients to thrombosis during a vulnerable period of reduced antiplatelet effect in the immediate post stenting period. Combination therapy with bivalirudin and prasugrel is conceptually attractive as the more rapid onset of action of prasugrel could potentially significantly diminish the vulnerable period, likely reducing the potential for acute stent thrombosis. The trials which have documented the efficacy of prasugrel as compared to clopidogrel have, in general, not reported on patients in whom bivalirudin was utilized. Currently, in the United States, bivalirudin is the most commonly used adjunctive agent used during PCI. Using light transmission aggregometry, this study will examine the inhibition of platelet aggregation in patients randomized to treatment with clopidogrel vs prasugrel during the vulnerable period following the discontinuation of bivalirudin therapy. The investigators anticipate that this study will document significant enhancement of inhibition of platelet aggregation in patients randomized to prasugrel treatment.

Conditions

Coronary Artery Disease

Keywords

Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; bivalirudin

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in ADP-mediated Platelet Aggregation, APP, SFFLRN, AYPGKF.

  To document the extent of inhibition of ADP mediated platelet aggregation following the discontinuation of bivalirudin therapy in patients treated with prasugrel as compared to patients treated with clopidogrel. The percent inhibition of platelet aggregation was measured by light transmission aggregometry of platelet-rich plasma in response to P2Y12 and PAR1 and PAR4 thrombin receptor agonists at baseline and at 1, 2, 4 and 16 h following the cessation of bivalirudin infusion. Platelet response to agonists: 20 mM ADP(P2Y12), 5 mM SFLLRN (PAR1), and 160 mM AYPGKF (PAR4) was performed. The magnitude of inhibition of platelet aggregation for each agonist was calculated as the mean final change from baseline in light transmission aggregometry at each time point.

  Baseline, 60, 120, 240, 960 mins following termination of bivalirudin infusion

Study Arms (2)

Prasugrel

ACTIVE COMPARATOR

Prasugrel oral loading dose of 60 mg administered preceding cardiac intervention

Drug: Prasugrel

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel oral loading dose of 600 mg administered preceding cardiac intervention

Drug: Clopidogrel

Interventions

Prasugrel DRUG

Patients will be randomized to prasugrel or clopidogrel to assess the effect of these drugs on inhibition of platelet aggregation following the cessation of bivalirudin therapy.

Also known as: Effient

Prasugrel

Clopidogrel DRUG

Clopidogrel 600 mg as a loading dose immediately prior to the start of procedure and 75 mg daily thereafter

Also known as: Plavix

Clopidogrel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent before initiation of any study related procedures
• Male or non-pregnant female aged 18 to ≤ 75 years
• Referred for PCI or structural cardiac intervention and planned to receive bivalirudin treatment
• Only subjects in whom the treating physician feels that clopidogrel and prasugrel are equivalent on the basis of available clinical literature will be included.

You may not qualify if:

• Currently receiving glycoprotein IIb/IIIa inhibitors.
• Have received prasugrel or clopidogrel within 2 weeks
• Serum creatinine level \>2.0
• Hypersensitivity to bivalirudin, prasugrel, clopidogrel or aspirin
• Currently on heparin administration or administered ≤ 4.5 h prior to intervention
• Thrombocytopenia (\<50,000/µL)
• Severe systemic hypertension defined as systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>110 mm Hg
• Body weight \< 60 kg
• Cardiogenic shock
• Acute pericarditis
• Active internal bleeding
• History of bleeding diathesis within previous thirty days
• Any history of intracranial hemorrhage, Transient ischemic attack (TIA ) or stroke
• Arteriovenous malformations or aneurysms
• Major surgical procedures or severe physical trauma within last thirty days.

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

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; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Carey Kimmelstiel, MD Director of the Adult Cardiac Catheterization Laboratory
• Organization: Tufts Medical Center

Ckimmelstiel@tuftsmedicalcenter.org

617-636-4504

Study Officials

• Carey Kimmelstiel, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 12, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 4, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-03

Locations

US (1)