Platelet ReactivityPhase 2/3NCT00827346
Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty
A Phase 2/3 study testing Clopidogrel in people with Platelet Reactivity, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial summary
Platelets are a major component of clot formation which can lead to clotting events such as heart attack. During treatment for a heart attack, doctors try to remove this blockage as quickly as possible so that the heart can recover and start to work properly again. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Platelet Reactivity
- What is being tested?
- Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2009to Apr 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Ischemic chest discomfort of greater than 30 minutes duration
- Onset of chest pain less than 12 hrs prior to entry into the study
- ST segment elevation of > 1 mm (0.1 mV) in two or more contiguous electrocardiographic leads (on a standard 12 lead ECG) or left bundle branch block not known to be old
Who cannot join
- Active bleeding
- GI or GU bleed within 2 weeks, or any major bleeding episode within 2 weeks
- Stroke within 90 days or intracranial bleeding at any time
- Major surgery or trauma within the past six weeks
- Uncontrolled hypertension (SBP > 200 mm Hg and/or DBP > 110 mm Hg despite treatment)
- Prolonged (>10 min) cardiopulmonary resuscitation
Show all 22Show fewer
- Inadequate vascular access
- PCI within the last 30 days
- Thrombolytic agents within the preceding 7 days
- GP IIb/IIIa antagonists within the preceding 7 days
- Coagulation disorder (i.e. INR >2.0, platelets <100,000 / mm3, or hematocrit <30%)
- Current warfarin treatment
- A subcutaneous therapeutic dose of any LMWH within 12 hours
- Intolerance to aspirin or clopidogrel
- Patient already on chronic clopidogrel therapy
- Other medical condition that is likely to result in death within 12 months
- Participation in a study with another investigational device or drug < four weeks
- Pregnancy
- Known severe renal impairment (creatinine clearance rate of less than 30 ml per minute)
- Sustained hypotension defined as SBP < 80 mmHg or the need for IV inotropes and/or intraaortic balloon counterpulsation to support the blood pressure
- Known severe contrast (dye) allergy
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Platelets are a major component of clot formation which can lead to clotting events such as heart attack. During treatment for a heart attack, doctors try to remove this blockage as quickly as possible so that the heart can recover and start to work properly again. The standard of care at the Heart Institute for patients having a heart attack is a procedure called a Percutaneous Coronary Angioplasty. A drug called Clopidogrel (Plavix) is routinely used prior to the angioplasty to prevent blood clots. Patients usually remain on Clopidogrel for at least one year following the angioplasty. Clopidogrel works by preventing the blood from forming sticky substances called platelets, which clump together to form clots. Despite the routine use of Clopidogrel, some patients still return to the hospital with another heart attack, or with more chest pain. There is a growing body of evidence that recurrence of these complications may be attributed to some patients having a poor response to Clopidogrel.
This pilot study will examine how platelets react to different doses of Clopidogrel given to patients having a heart attack.
Read the detailed description
Platelets are a major component of clot formation which can lead to thrombotic events. Antiplatelet agents have been found to reduce cardiovascular events in different clinical settings. The commonest agent that has been used is aspirin which works by inhibiting the cyclooxygenase pathway within the platelet and consequently preventing the release of tromboxane A2. A second group of agents called thienopyridines can inhibit platelets by blocking the P2Y12 receptor. Clopidogrel (Plavix) is currently a widely used thienopyridine that has been used for the treatment of patients presenting with the acute coronary syndrome and patients undergoing percutaneous coronary angioplasty (PCI). Antiplatelet therapy has reduced the occurrence of thrombotic events following PCI, including myocardial infarction and stent thrombosis. However, despite dual therapy with aspirin and clopidogrel, a significant number of patients continue to experience cardiovascular events. There is a now growing body of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel and that persistence of enhanced platelet reactivity despite the use of clopidogrel is believed to be clinically relevant.1 The mechanisms leading to poor clopidogrel effects are not fully explained.
Our pilot study will use the VerifyNow device as an ex vivo method to measure platelet inhibition in patients treated with clopidogrel in the setting of STEMI. Since July 2004, the standard of care at the University of Ottawa Heart Institute for the treatment of STEMI has been primary PCI in which all patients receive aspirin 160 mg po either in the field or on arrival in the emergency department and clopidogrel 600 mg po given on arrival to the hospital. Little is known of the pharmacokinetics of clopidogrel in the setting of STEMI. Clopidogrel must be absorbed and activated by the liver to be effective. The physiological mechanisms for these steps may be greatly disturbed in patients presenting with STEMI. Therefore, the purpose of this study will be to examine the degree of platelet inhibition at various time points in this select patient population using the current 600 mg dose of clopidogrel and comparing this dose to other doses of clopidogrel to determine the optimal loading dose in the context of STEMI.
- Conditions
- Platelet Reactivity
- Being tested
- Clopidogrel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
600 mg now
ClopidogrelDrug
600 mg now and 600 mg in 3 hours
ClopidogrelDrug
900 mg now
ClopidogrelDrug
600 mg now and 300 mg in 3 hours
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | 600-mg double dose Receives: Drug: Clopidogrel |
| Group 2 | Active comparator | 600/600-mg double loading dose (first dose 600 mg given immediately upon arrival at the hospital and the second dose 600 mg, 3 hours after the first loading dose for a total of 900 mg Receives: Drug: Clopidogrel |
| Group 3 | Active comparator | Clopidogrel 900mg Receives: Drug: Clopidogrel |
| Group 4 | Active comparator | First dose 600 mg given immediately upon arrival at the hospital and the second dose 300 mg, 3 hours after the first loading dose for a total of 900 mg Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this randomized pilot study is to evaluate the inhibition of platelet aggregation (IPA) amongst 4 different loading doses of clopidogrel in patients with STEMI treated with bivalirudin as anticoagulant for PCI
Measured: Up to 48hrs
Secondary outcomes (2)
Clinical events (death reinfarction, stroke, bleeding)
Measured: Up to 6 months
The percent TIMI grade 3 coronary flow at first contrast injection on the base-line angiogram, to TIMI flow after the PCI,
Measured: Pre and post ballon injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Platelet ReactivityStudies of the same condition, open and under way.
- More trials run by Ottawa Heart Institute Research CorporationThe 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 2/3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Investigators
- Michel R Le May, MD FRCPC FACC, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00827346
- Sponsor's protocol ID
- MRL-A2
- Other IDs
- 2008239-01H
- Status last verified
- Apr 2011
- First submitted
- 20 Jan 2009
- Last updated
- 29 Apr 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty
- ClinicalTrials.gov ID
- NCT00827346
- Acronym / sponsor ID
- MRL-A2
- Conditions
- Platelet Reactivity
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 22 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Platelets are a major component of clot formation which can lead to clotting events such as heart attack. During treatment for a heart attack, doctors try to remove this blockage as quickly as possible so that the heart can recover and start to work properly again. The standard of care at the Heart Institute for patients having a heart attack is a procedure called a Percutaneous Coronary Angioplasty. A drug called Clopidogrel (Plavix) is routinely used prior to the angioplasty to prevent blood clots. Patients usually remain on Clopidogrel for at least one year following the angioplasty. Clopidogrel works by preventing the blood from forming sticky substances called platelets, which clump together to form clots. Despite the routine use of Clopidogrel, some patients still return to the hospital with another heart attack, or with more chest pain. There is a growing body of evidence that recurrence of these complications may be attributed to some patients having a poor response to Clopidogrel.
This pilot study will examine how platelets react to different doses of Clopidogrel given to patients having a heart attack.
Detailed description
Platelets are a major component of clot formation which can lead to thrombotic events. Antiplatelet agents have been found to reduce cardiovascular events in different clinical settings. The commonest agent that has been used is aspirin which works by inhibiting the cyclooxygenase pathway within the platelet and consequently preventing the release of tromboxane A2. A second group of agents called thienopyridines can inhibit platelets by blocking the P2Y12 receptor. Clopidogrel (Plavix) is currently a widely used thienopyridine that has been used for the treatment of patients presenting with the acute coronary syndrome and patients undergoing percutaneous coronary angioplasty (PCI). Antiplatelet therapy has reduced the occurrence of thrombotic events following PCI, including myocardial infarction and stent thrombosis. However, despite dual therapy with aspirin and clopidogrel, a significant number of patients continue to experience cardiovascular events. There is a now growing body of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel and that persistence of enhanced platelet reactivity despite the use of clopidogrel is believed to be clinically relevant.1 The mechanisms leading to poor clopidogrel effects are not fully explained.
Our pilot study will use the VerifyNow device as an ex vivo method to measure platelet inhibition in patients treated with clopidogrel in the setting of STEMI. Since July 2004, the standard of care at the University of Ottawa Heart Institute for the treatment of STEMI has been primary PCI in which all patients receive aspirin 160 mg po either in the field or on arrival in the emergency department and clopidogrel 600 mg po given on arrival to the hospital. Little is known of the pharmacokinetics of clopidogrel in the setting of STEMI. Clopidogrel must be absorbed and activated by the liver to be effective. The physiological mechanisms for these steps may be greatly disturbed in patients presenting with STEMI. Therefore, the purpose of this study will be to examine the degree of platelet inhibition at various time points in this select patient population using the current 600 mg dose of clopidogrel and comparing this dose to other doses of clopidogrel to determine the optimal loading dose in the context of STEMI.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: Clopidogrel600-mg double dose |
| Group 2 | Active comparator | Drug: Clopidogrel600/600-mg double loading dose (first dose 600 mg given immediately upon arrival at the hospital and the second dose 600 mg, 3 hours after the first loading dose for a total of 900 mg |
| Group 3 | Active comparator | Drug: ClopidogrelClopidogrel 900mg |
| Group 4 | Active comparator | Drug: ClopidogrelFirst dose 600 mg given immediately upon arrival at the hospital and the second dose 300 mg, 3 hours after the first loading dose for a total of 900 mg |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Ischemic chest discomfort of greater than 30 minutes duration
- Onset of chest pain less than 12 hrs prior to entry into the study
- ST segment elevation of > 1 mm (0.1 mV) in two or more contiguous electrocardiographic leads (on a standard 12 lead ECG) or left bundle branch block not known to be old
Key exclusion criteria (22 listed)
- Active bleeding
- GI or GU bleed within 2 weeks, or any major bleeding episode within 2 weeks
- Stroke within 90 days or intracranial bleeding at any time
- Major surgery or trauma within the past six weeks
- Uncontrolled hypertension (SBP > 200 mm Hg and/or DBP > 110 mm Hg despite treatment)
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 |
|---|---|---|
| Clopidogrel600 mg now | Drug | Group 1 |
| Clopidogrel600 mg now and 600 mg in 3 hours | Drug | Group 2 |
| Clopidogrel900 mg now | Drug | Group 3 |
| Clopidogrel600 mg now and 300 mg in 3 hours | Drug | Group 4 |
Primary outcome
The primary objective of this randomized pilot study is to evaluate the inhibition of platelet aggregation (IPA) amongst 4 different loading doses of clopidogrel in patients with STEMI treated with bivalirudin as anticoagulant for PCI
Time frame: Up to 48hrs
2 secondary outcomes
Clinical events (death reinfarction, stroke, bleeding)
Time frame: Up to 6 months
The percent TIMI grade 3 coronary flow at first contrast injection on the base-line angiogram, to TIMI flow after the PCI,
Time frame: Pre and post ballon injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2011.
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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.
Michel R Le May, MD FRCPC FACC principal investigator
Ottawa Heart Institute Research Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Clopidogrel in people with Platelet Reactivity, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
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 22 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 29 Apr 2011. 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 Canada. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 primary objective of this randomized pilot study is to evaluate the inhibition of platelet aggregation (IPA) amongst 4 different loading doses of clopidogrel in patients with STEMI treated with bivalirudin as anticoagulant for PCI (time frame: Up to 48hrs). 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 29 Apr 2011.