Ticagrelor Monotherapy Compared to Aspirin Monotherapy in Patients With History of ACS (FMD_ACS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03881943|
Recruitment Status : Completed
First Posted : March 20, 2019
Last Update Posted : March 20, 2019
|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|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Ticagrelor or Aspirin|
|Masking:||Double (Participant, Investigator)|
|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|
Active Comparator: Ticagrelor
Ticagrelor 60mg BD for 3 months
Drug: Ticagrelor 60 mg
Potent antiplatelet agent, 60mg twice daily for 3 months
Other Name: Brilinta
Active Comparator: Aspirin
Aspirin 100mg daily for 3 months
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
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
|Prof. HF Tse|
|Hong Kong, China|