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Platelet Inhibition in Patients With Systolic Heart Failure

Primary Purpose

Systolic Heart Failure

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Prasugrel 10 mg daily x 2 weeks
Clopidogrel 75 mg daily x 2 weeks
Sponsored by
University of Nebraska
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systolic Heart Failure focused on measuring Heart failure, Antiplatelet therapy, Platelet aggregation, Clopidogrel, Prasugrel

Eligibility Criteria

19 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients 19 to 74 years of age.
  • Patients with a left ventricular ejection fraction <35% by echocardiogram, SPECT myocardial perfusion study, cardiac MRI, cardiac computerized tomographic angiogram or invasive left ventricular angiogram within the last 6 months.
  • Patients with NYHA Class III-IV heart failure at the time of enrollment.

Exclusion Criteria:

  • Recent hospitalization within 30 days
  • Patients expected to undergo major surgery or PCI in the next 30 days
  • Patients taking clopidogrel, prasugrel, ticagrelor, ticlopidine, or cilostazol
  • Patients listed for heart transplantation or having left ventricular assist device placement
  • Patients with known allergy to either medication
  • Patients with prior history of stroke or transient ischemic attack
  • Patients with known intracranial neoplasm, aneurysm, or arteriovenous malformation
  • Patients with a history of bleeding requiring hospitalization for treatment
  • Patients taking oral anticoagulants
  • Patients with body weight <60 kg
  • Women who are pregnant or breastfeeding
  • Patients with hemoglobin <10 mg/dl or platelet count <100,000/ul at baseline
  • Patients with known clotting or platelet disorders
  • Patients with a baseline INR > 1.4
  • Patients with liver function tests (AST or ALT) > 2 times normal
  • Patients with a suspected change in their use of aspirin during the study (starting, stopping, or changing dose of aspirin)
  • Patients unwilling to consent to CYP2C19 genetic testing.

Sites / Locations

  • University of Nebaska Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Prasugrel

Clopidogrel

Arm Description

Prasugrel oral 10 mg once daily for 2 weeks

Clopidogrel oral 75 mg once daily for 2 weeks

Outcomes

Primary Outcome Measures

The Change in Platelet Aggregation Measured by the Accumetrics (VerifyNow P2Y12) Assay Between Baseline and Each Antiplatelet Medication

Secondary Outcome Measures

The Change in Light Transmission Aggregometry (LTA)Between Baseline and Each Antiplatelet Medication
The Change in Platelet Activation Assay (VASP)Between Baseline and Each Antiplatelet Medication

Full Information

First Posted
December 12, 2012
Last Updated
September 26, 2023
Sponsor
University of Nebraska
Collaborators
Daiichi Sankyo, Inc., Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT01765400
Brief Title
Platelet Inhibition in Patients With Systolic Heart Failure
Official Title
Platelet Reactivity With Clopidogrel Versus Prasugrel in Patients With Systolic Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 15, 2013 (Actual)
Primary Completion Date
December 1, 2015 (Actual)
Study Completion Date
December 28, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
Collaborators
Daiichi Sankyo, Inc., Eli Lilly and Company

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators aim to determine if patients with systolic heart failure treated with prasugrel achieve greater platelet inhibition compared to those treated with clopidogrel.
Detailed Description
Thienopyridine antiplatelet agents are an important component of therapy for management of acute coronary syndrome (ACS). Dual antiplatelet therapy with a thienopyridine, most commonly clopidogrel, and aspirin is widely used in the management of ACS to prevent major adverse cardiovascular events. Despite the benefits of this regimen, many patients continue to develop atherothrombotic events while on this regimen. Various reasons including inter-patient variability, delayed onset of action, and the obtainable antiplatelet activity of clopidogrel have been described as potential causes of the limited efficacy in preventing recurrent events. The Trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction (TRITON-TIMI 38) showed that patients with moderate-to-high-risk ACS scheduled for percutaneous coronary intervention (PCI) treated with prasugrel had decreased cardiovascular events compared to clopidogrel. Clopidogrel is a prodrug that requires two hepatic conversion steps by the cytochrome (CYP)P450 enzyme system. The need for CYP450 involvement is known to contribute to the variable response of platelet inhibition demonstrated with clopidogrel. Although prasugrel is also a thienopyridine, it only requires hepatic CYP450 enzymes for one conversion step, and is converted to the active metabolite more efficiently. Therefore, prasugrel provides significantly more potent platelet inhibition compared to clopidogrel. Patients with advanced systolic heart failure commonly have elevated hepatic venous pressures that can cause hepatic congestion and hypoperfusion resulting in impaired hepatic function. The elevated hepatic venous pressure predominantly affects the hepatic centrilobular cells which contain the highest concentration of cytochrome P-450 (CYP450) enzyme system. Hence patients with advanced heart failure may convert less clopidogrel to the active metabolite and subsequently produce less platelet inhibition compared to prasugrel. Since prasugrel only requires the CYP450 system for one conversion step, the impact of hepatic congestion should be limited for heart failure patients treated with prasugrel. The phase 3, multi-center TRITON-TIMI 38 trial comparing clopidogrel and prasugrel showed that in an unselected patient population presenting with ACS, prasugrel achieved greater cardiovascular event reduction that was attributed to more robust platelet inhibition. Hence, we designed this trial to prospectively test the hypothesis that systolic heart failure patients with increased circulating catecholamines and possible abnormal functioning of CYP450 system treated with prasugrel will achieve greater platelet reactivity inhibition compared to those treated with clopidogrel.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systolic Heart Failure
Keywords
Heart failure, Antiplatelet therapy, Platelet aggregation, Clopidogrel, Prasugrel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prasugrel
Arm Type
Active Comparator
Arm Description
Prasugrel oral 10 mg once daily for 2 weeks
Arm Title
Clopidogrel
Arm Type
Active Comparator
Arm Description
Clopidogrel oral 75 mg once daily for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Prasugrel 10 mg daily x 2 weeks
Intervention Type
Drug
Intervention Name(s)
Clopidogrel 75 mg daily x 2 weeks
Primary Outcome Measure Information:
Title
The Change in Platelet Aggregation Measured by the Accumetrics (VerifyNow P2Y12) Assay Between Baseline and Each Antiplatelet Medication
Time Frame
Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel, Change From Baseline at Week 2 Reported
Secondary Outcome Measure Information:
Title
The Change in Light Transmission Aggregometry (LTA)Between Baseline and Each Antiplatelet Medication
Time Frame
Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel
Title
The Change in Platelet Activation Assay (VASP)Between Baseline and Each Antiplatelet Medication
Time Frame
Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients 19 to 74 years of age. Patients with a left ventricular ejection fraction <35% by echocardiogram, SPECT myocardial perfusion study, cardiac MRI, cardiac computerized tomographic angiogram or invasive left ventricular angiogram within the last 6 months. Patients with NYHA Class III-IV heart failure at the time of enrollment. Exclusion Criteria: Recent hospitalization within 30 days Patients expected to undergo major surgery or PCI in the next 30 days Patients taking clopidogrel, prasugrel, ticagrelor, ticlopidine, or cilostazol Patients listed for heart transplantation or having left ventricular assist device placement Patients with known allergy to either medication Patients with prior history of stroke or transient ischemic attack Patients with known intracranial neoplasm, aneurysm, or arteriovenous malformation Patients with a history of bleeding requiring hospitalization for treatment Patients taking oral anticoagulants Patients with body weight <60 kg Women who are pregnant or breastfeeding Patients with hemoglobin <10 mg/dl or platelet count <100,000/ul at baseline Patients with known clotting or platelet disorders Patients with a baseline INR > 1.4 Patients with liver function tests (AST or ALT) > 2 times normal Patients with a suspected change in their use of aspirin during the study (starting, stopping, or changing dose of aspirin) Patients unwilling to consent to CYP2C19 genetic testing.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul P Dobesh, PharmD
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebaska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States

12. IPD Sharing Statement

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Platelet Inhibition in Patients With Systolic Heart Failure

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