Ticagrelor Monotherapy Compared to Aspirin Monotherapy in Patients With History of ACS (FMD_ACS)
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| ClinicalTrials.gov Identifier: NCT03881943 |
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Recruitment Status :
Completed
First Posted : March 20, 2019
Last Update Posted : March 20, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Coronary Syndrome | Drug: Ticagrelor 60 mg Drug: Aspirin 100 MG Oral Tablet, Enteric Coated | Phase 4 |
Acute coronary syndrome (ACS) is a disease with high mortality, morbidity and economic burden. Usually, it is caused by ischemic heart disease and atherosclerotic plaque rupture in the coronary arteries causing platelet activation, aggregation and thrombus formation. For decades, antiplatelet agents are the cornerstones of management of ACS and several clinical trials have confirmed greater clinical efficacy of dual antiplatelet therapy with clopidogrel and aspirin (ASA) versus ASA alone in patients with acute coronary syndromes (ACS) for up to a year of therapy. Ticagrelor (AZD6140) is a reversible, potent, oral adenosine diphosphate (ADP) P2Y12 receptor blocker which has stronger antiplatelet activity than clopidogrel. Data from PLATO, a Phase III pivotal efficacy and safety study of ticagrelor, have demonstrated superiority of ticagrelor 90 mg twice daily over clopidogrel 75 mg daily with a duration of up to 12 months in the prevention of fatal and non-fatal cardiovascular event in ACS patients on ASA.
In PLATO, ticagrelor was superior to clopidogrel in reducing the rate of the composite efficacy endpoint of CV death, MI, or stroke after ACS events. Furthermore, compared to clopidogrel, ticagrelor decreased the rate of death from any cause. PLATO-defined Major bleeding (primary safety endpoint) for ticagrelor did not differ significantly from that of clopidogrel but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting.
The favourable results lead to approval of use of ticagrelor as Class I indication in ACS patients for up to one year in addition to ASA in ACC/AHA and European guidelines. After one year of DAPT, patients typically remained on single antiplatelet agent with ASA monotherapy being the conventional treatment. However, these patients are still at heightened risk of recurrent atherothrombotic events. The recent PEGASUS TIMI 54 trial investigated the use of ticagrelor in addition to aspirin in stable patients with prior myocardial infarction one to three years ago. It demonstrated ticagrelor either 90mg BD or 60mg BD significantly reduced the risk of cardiovascular death, MI and stroke compared with placebo; ticagrelor 60mg BD. However, the use of ticagrelor is also associated with higher risks of major bleeding; ticagrelor 60mg BD, HR 2.32.
As the antithrombotic benefit of stronger antiplatelet effects of DAPT is offset by higher bleeding risk, it is reasonable to assume that a single potent antiplatelet agent such as ticagrelor may lead to better clinical outcome than ASA with less increase in bleeding risk when compared with DAPT. In addition to its antiplatelet effects, ticagrelor has been shown to improve endothelial function, increase plasma adenosine level, increase coronary blood flow, stabilize coronary plaques and reduce inflammation. These pleiotropic effects may lead to further clinical benefit of ticagrelor over other antiplatelet agents such as ASA and clopidogrel. Endothelial function as measured by flow mediated dilatation of brachial artery is a non-invasively measurable surrogate marker of adverse cardiovascular events. Adenosine is a purine nucleoside which has favourable effects on coronary vasodilatation, endothelial progenitor cell migration and ischemia-reperfusion injury while adenosine plasma activity can be measured by liquid chromatography.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 200 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Ticagrelor or Aspirin |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Single Center Trial to Assess the Endothelial Function With Ticagrelor Monotherapy Compared to Aspirin Monotherapy in Patients With History of Acute Coronary Syndrome |
| Actual Study Start Date : | January 2017 |
| Actual Primary Completion Date : | December 21, 2018 |
| Actual Study Completion Date : | December 21, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Ticagrelor
Ticagrelor 60mg BD for 3 months
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Drug: Ticagrelor 60 mg
Potent antiplatelet agent, 60mg twice daily for 3 months
Other Name: Brilinta |
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Active Comparator: Aspirin
Aspirin 100mg daily for 3 months
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Drug: Aspirin 100 MG Oral Tablet, Enteric Coated
antiplatelet agent, 100mg once daily for 3 months
Other Name: Cartia |
- Endothelial Function [ Time Frame: 3 months ]the flow mediated dilatation of brachial artery at baseline and 3 months after randomization. Demonstrate brachial diameters, the measurement will be presented in absolute FMD millimeter (FMDmm). The report value should be present in FMD percentage (FMD%) as the mean of baseline measurement minus the mean of 3 months measurement then divided by the 3 months measurement.
- Plasma adenosine level Platelet function parameters Endothelial progenitor cell count Biomarkers such as highly sensitive troponin [ Time Frame: 3 months ]collect the blood sample to test the Plasma adenosine level Platelet function parameters Endothelial progenitor cell count Biomarkers such as highly sensitive troponin at baseline and 3 months after randomization. The unit of the test should be nmol/L
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Men and women aged 18 years or above.
- Documented history of presumed spontaneous ACS (excluding known peri-procedural or definite secondary MI [eg, due to profound hypotension, hypertensive emergency, tachycardia, or profound anemia]) with their most recent MI occurring 18 months or more prior to randomization
- Patient currently prescribed and tolerating ASA
- Females of child-bearing potential (ie, who are not chemically or surgically sterilized or who are not post-menopause) must have a negative urine pregnancy test at enrollment (to be confirmed by blood pregnancy test at the central lab.) Females of child-bearing potential must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator.
- Written informed consent prior to any study specific procedures.
Exclusion Criteria:
- Recurrent cardiovascular event (ACS, stroke and unplanned revascularization) after the index ACS
- Planned use of ADP receptor blockers (eg, clopidogrel, ticlopidine, prasugrel), dipyridamole, or cilostazol
- Planned coronary, cerebrovascular, or peripheral arterial revascularization
- Concomitant oral or intravenous therapy with strong cytochrome P450 3A (CYP3A) inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study - Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice - Substrates with narrow therapeutic index: cyclosporine, quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily
- Concomitant use of vasoactive drugs or vasoactive drugs cannot be stopped.
- Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
- Patients with known bleeding diathesis or coagulation disorder
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Patients with:
- Concomitant active pathological bleeding,
- A history of intracranial bleed at any time,
- A central nervous system tumour or intracranial vascular abnormality (eg, aneurysm, arteriovenous malformation) at any time,
- Intracranial or spinal cord surgery within 5 years, or
- A gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days
- History of ischemic stroke at any time
- Patients considered to be at risk of bradycardic events ([eg, known sick sinus syndrome or second or third degree atrioventricular (AV) block]) unless already treated with a permanent pacemaker
- Coronary-artery bypass grafting in the past 5 years, unless the patient has experienced a spontaneous MI subsequent to the bypass surgery.
- Known severe liver disease (eg, ascites or signs of coagulopathy)
- Renal failure requiring dialysis or anticipated need for dialysis during the course of the study
- Hypersensitivity to ticagrelor or any excipients
- Pregnancy or lactation
- Life expectancy < 1 year
- Any condition which in the opinion of the Investigator would make it unsafe or unsuitable for the patient to participate in this study (eg, active malignancy other than squamous cell or basal cell skin cancer)
- Concern for inability of the patient to comply with study procedures and/or follow up (eg, alcohol or drug abuse)
- Participation in previous study with ticagrelor if treated with ticagrelor. Previous randomization in the present study
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the preceding 30 days
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03881943
| China | |
| Prof. HF Tse | |
| Hong Kong, China | |
| Responsible Party: | Tse Hung Fat, Professor, The University of Hong Kong |
| ClinicalTrials.gov Identifier: | NCT03881943 |
| Other Study ID Numbers: |
FMD_1.3 |
| First Posted: | March 20, 2019 Key Record Dates |
| Last Update Posted: | March 20, 2019 |
| Last Verified: | March 2019 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Acute Coronary Syndrome Syndrome Disease Pathologic Processes Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Aspirin Ticagrelor Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents |