Systolic Heart FailurePhase 4NCT01765400
Platelet Inhibition in Patients With Systolic Heart Failure
A Phase 4 study testing Prasugrel 10 mg daily x 2 weeks and Clopidogrel 75 mg daily x 2 weeks in people with Systolic Heart Failure, run by University of Nebraska at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- Systolic Heart Failure
- What is being tested?
- Prasugrel 10 mg daily x 2 weeks and Clopidogrel 75 mg daily x 2 weeks
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2013to 28 Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebaska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Platelet Reactivity With Clopidogrel Versus Prasugrel in Patients With Systolic Heart Failure
The investigators aim to determine if patients with systolic heart failure treated with prasugrel achieve greater platelet inhibition compared to those treated with clopidogrel.
Read the 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.
- Conditions
- Systolic Heart Failure
- Being tested
- Prasugrel 10 mg daily x 2 weeks, Clopidogrel 75 mg daily x 2 weeks
- Keywords
- Heart failure, Antiplatelet therapy, Platelet aggregation, Clopidogrel, Prasugrel
- Medical subject headings
- Heart Failure, Systolic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prasugrel 10 mg daily x 2 weeksDrug
Clopidogrel 75 mg daily x 2 weeksDrug
| Study group | Role | What they receive |
|---|---|---|
| Prasugrel | Active comparator | Prasugrel oral 10 mg once daily for 2 weeks Receives: Drug: Prasugrel 10 mg daily x 2 weeks |
| Clopidogrel | Active comparator | Clopidogrel oral 75 mg once daily for 2 weeks Receives: Drug: Clopidogrel 75 mg daily x 2 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Change in Platelet Aggregation Measured by the Accumetrics (VerifyNow P2Y12) Assay Between Baseline and Each Antiplatelet Medication
Measured: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel, Change From Baseline at Week 2 Reported
Secondary outcomes (2)
The Change in Light Transmission Aggregometry (LTA)Between Baseline and Each Antiplatelet Medication
Measured: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel
The Change in Platelet Activation Assay (VASP)Between Baseline and Each Antiplatelet Medication
Measured: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study start15 May 2013
- Primary completion1 Dec 2015
- Study completion28 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Systolic Heart FailureStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo, Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Paul P Dobesh, PharmD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765400
- Sponsor's protocol ID
- 0574-11-FB
- Status last verified
- Sep 2023
- First submitted
- 12 Dec 2012
- Last updated
- 10 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet Reactivity With Clopidogrel Versus Prasugrel in Patients With Systolic Heart Failure
- ClinicalTrials.gov ID
- NCT01765400
- Acronym / sponsor ID
- 0574-11-FB
- Conditions
- Systolic Heart Failure
- Keywords
- Heart failure, Antiplatelet therapy, Platelet aggregation, Clopidogrel, Prasugrel
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- Daiichi Sankyo, Eli Lilly and Company
- Study start
- 15 May 2013 (actual)
- Primary completion
- 1 Dec 2015 (actual)
- Study completion
- 28 Dec 2015 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Posted 30 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prasugrel | Active comparator | Drug: Prasugrel 10 mg daily x 2 weeksPrasugrel oral 10 mg once daily for 2 weeks |
| Clopidogrel | Active comparator | Drug: Clopidogrel 75 mg daily x 2 weeksClopidogrel oral 75 mg once daily for 2 weeks |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prasugrel 10 mg daily x 2 weeks | Drug | Prasugrel |
| Clopidogrel 75 mg daily x 2 weeks | Drug | Clopidogrel |
Primary outcome
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
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul P Dobesh, PharmD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prasugrel 10 mg daily x 2 weeks and Clopidogrel 75 mg daily x 2 weeks in people with Systolic Heart Failure, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.