85 Clinical Trials for Various Conditions
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a drug-drug interaction when ticagrelor is administered prior to cangrelor infusion.
Recent studies have shown that withdrawing aspirin and maintaining P2Y12 inhibitor monotherapy for up to 12 months post-PCI, after a brief period of DAPT, reduces bleeding without increasing ischemic harm. Such effects have shown to of particular benefit in patients with diabetes mellitus (DM). However, if an aspirin-free approach can be considered after this time frame is a matter of debate. The aim of this study is to assess the PD effects of ticagrelor 60 mg with and without aspirin therapy in CAD patients and to compare this with a standard DAPT regimen of aspirin plus clopidogrel.
Hypothesis The primary question the investigators propose to answer is whether all patients undergoing percutaneous coronary intervention (PCI) with stent deployment who receive chewed ticagrelor will demonstrate more rapid drug absorption and decreased platelet reactivity as compared to integral pill form 1 hour after drug administration.
The purpose of the study is to Evaluate the Effect of Ticagrelor versus Placebo in Reducing the Rate of Vaso-Occlusive Crises in Paediatric Patients with Sickle Cell Disease
Polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme has been consistently shown to modulate clopidogrel response. Accordingly, the Food and Drug Administration (FDA) has issued a warning on the potential for reduced efficacy of clopidogrel among carriers of loss-of-function alleles (LOF) for CYP2C19 and suggest considering alternative antiplatelet therapies for these individuals. The pharmacodynamic (PD) effects of prasugrel and ticagrelor are not affected by CYP2C19 genetic polymorphisms. However, to date there are no head-to-head PD comparisons between these agents among patients with different CYP2C19 genetic polymorphisms, which is currently under investigation in CAD patients undergoing PCI at UF Health-Jacksonville (UFJ 2014-12, NCT 02065479). In order to rule out play of chance findings, pharmacogenetic investigations require external validation cohorts to support the study findings. Therefore, the present randomized study is designed to serve as an external validation cohort conducted in patients with established CAD not undergoing PCI testing the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 LOF allele carriers.
To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in patients with DM who are known to have impaired response to clopidogrel therapy. Since DM patients frequently require elective PCI due to chronic progression of CAD (and not solely because of an acute thrombotic complication), and clopidogrel remains the guideline recommended P2Y12 inhibiting therapy for these patients, understanding the PD effects of the ticagrelor 60 mg bid regimen in this setting is an unmet clinical need. This is also in light of the ongoing THEMIS trial which is specifically evaluating the impact of the ticagrelor 60 mg bid dosing regimen in type 2 DM patients without a prior major CV event.
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.
This is an open label study to assess the improvement in the Disease Activity Score for 28-joint counts (DAS28) with ticagrelor given at 90 mg twice daily in patients with RA who have active disease despite MTX therapy (as defined by the inclusion/exclusion criteria). There will also be a cross sectional analysis of baseline platelet activity in subjects with rheumatoid arthritis and osteoarthritis. Subjects in the OA cohort will not receive any study medication, and will only have one study visit. Patients will receive 90 mg ticagrelor orally bid. The patients will receive drug for 30-days. Methotrexate dose will remain stable throughout the study duration.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the long-term secondary prevention of atherothrombotic events in patients with myocardial infarction (MI). However, rates of ischemic recurrences remain high, which may be in part due to the fact that other platelet signaling pathways, such as thrombin-induced platelet aggregation, continue to be activated. Vorapaxar is a protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of thrombin-mediated platelet aggregation. It is approved for clinical use by the Food and Drug Administration for the reduction of thrombotic cardiovascular events in patients with a history of MI or with peripheral arterial disease. However, to date clinical trial experience with vorapaxar has been almost exclusively with the P2Y12 receptor inhibitor clopidogrel and the effects of vorapaxar in combination with antiplatelet therapy including prasugrel or ticagrelor, is largely unexplored. Further, the role of vorapaxar as part of a dual antithrombotic treatment regimen, in addition to a novel P2Y12 receptor inhibitor, with withdrawal of aspirin, represents another important area of clinical interest as it has the potential to maximize ischemic protection while reducing the risk of bleeding. The proposed prospective, randomized, parallel-design, open label, study conducted in a real world clinical setting of post-MI patients will aim to assess the pharmacodynamic effects of vorapaxar in addition to antiplatelet therapy with a novel P2Y12 receptor inhibitor (prasugrel or ticagrelor) with and without aspirin.
Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events. Importantly, DM is a key risk factor for the development of chronic kidney disease (CKD), which further enhances atherothrombotic risk. Clopidogrel is the most widely used platelet P2Y12 receptor inhibitor. However, despite its clinical benefit, patients with DM and CKD frequently experience recurrent atherothrombotic events. Ticagrelor is an oral, reversible, non-competitive P2Y12 receptor inhibitor with more potent and consistent platelet inhibition than clopidogrel. In large-scale clinical investigation, ticagrelor significantly reduced ischemic events to a greater extent than clopidogrel, a finding that was consistent also among DM patients. To date there has been no analysis on the efficacy of ticagrelor in DM patients according to CKD status. Moreover, although pharmacodynamic (PD) studies showed enhanced platelet inhibition associated with ticagrelor, it is unknown how this may be affected by CKD status. Ultimately, how PK/PD profiles of different ticagrelor dosing regimens may be affected by DM and CKD status is also unknown. The proposed study is aimed to show the impact of CKD status among patients with DM and coronary artery disease) CAD on PD and PK profiles of ticagrelor used at 2 doses (90mg bid and 60mg bid) in the setting of a prospective, randomized, cross-over trial.
The purpose of this study is to determine whether ticagrelor is effective in reducing the number of days of pain, intensity of pain, and reducing the use of analgesics due to sickle cell disease
This is an interventional study assessing the effectiveness of Ticagrelor on the reduction of thrombus burden using optical coherence tomography in patients undergoing peripheral artery stenting.
This study is a randomized, placebo-controlled, single blind clinical trial. Seventy patients with ESRD on chronic HD and a functioning AVF will be recruited. The following data will be documented on each patient: 1-Age/gender/race/body weight/cause of ESRD 2-Vintage of HD 3-Time since access was placed 4-Type and place of access and blood flow rate of access 5-History of prior access problems 6-Comorbid conditions (Hypertension, coronary artery disease, Diabetes Mellitus, Bleeding problems, peripheral vascular disease). 7-Current medications (Coumadin, Erythropoiesis stimulating agents, heparin, other antiplatelets, digoxin, statins). Patients will be randomized into two groups to receive: Group 1: Ticagrelor 90 mg PO BID Group 2: Placebo drug PO BID.
The hypothesis being that both aspirin-ticagrelor and ticagrelor monotherapy will be superior to aspirin monotherapy in the reduction of whole blood viscosity at the end of each 4 week treatment period. Study participants will be randomized into 3 groups, and each group will receive each of 3 treatments in the cross-over study. At the end of each individual 4 week treatment period the investigators will determine whether there are differences in low and high shear rate dependent viscosity and investigate the effect of the treatment on peripheral arterial blood flow using pulse volume recordings, ankle brachial index and toe pressures. Subjects will be eligible if they have ankle-brachial index less than or equal to 0.85, or if a patient's blood vessels are calcified, patients will have toe-brachial index less than or equal to 0.6 performed using continuous-wave Doppler.
The purpose of this study is to estimate the risk of bleeding with rivaroxaban, compared with acetylsalicylic acid (ASA), in addition to a single antiplatelet/ platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor agent: clopidogrel or ticagrelor), in participants with a recent acute coronary syndrome (ACS: including ST segment elevation myocardial infarction \[STEMI\] and non-ST-segment elevation acute coronary syndrome \[NSTE-ACS\]).
The purpose of this pilot study is to establish the rate of cardiovascular events in patients with elevated troponins levels after major, non-cardiac surgery and to evaluate the efficacy and safety of FDA approved study drug (ticagrelor) compared to aspirin in these patients. Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within 3 days after non-cardiac surgery may occur in 10-24% of patients and is associated with an increased risk of mortality at 30 days and 1 year. There are no current guidelines for care of patients with elevated troponin levels in the absence of acute coronary syndrome. This study will assess if the increased risk of these patients is modifiable by an anti-platelet medication and evaluate the safety of this medication. Patients will be randomized in an open label fashion to receive ticagrelor (anti-platelet medication) or 81 mg. aspirin. Patients will be followed on study treatment for 12 months, with the last contact at one month post treatment discontinuation.
The purpose of this study is to compare the use of ticagrelor alone versus ticagrelor and aspirin together. Both ticagrelor and aspirin stop platelets from sticking together and forming a blood clot that could block blood flow to the heart. This study will look to determine the effectiveness and safety of ticagrelor alone, compared to ticagrelor plus aspirin in reducing clinically relevant bleeding and in reducing ischemic adverse events among high-risk patients who have had a percutaneous intervention with at least one drug-eluting stent. A patient is considered high-risk if they meet certain clinical and/or anatomic criteria. Up to 9000 subjects will be enrolled at the time of their index PCI. Subjects meeting randomization eligibility criteria at 3 months post enrollment will be randomized to either ticagrelor plus aspirin or ticagrelor plus placebo for an additional 12 months. Follow-up clinic visits will be performed at 3 months, 9 months and 15 months post enrollment.
To compare the effect of ticagrelor versus aspirin on the change in peak walking time, evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in patients with peripheral artery disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.
Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to shorten this period could be useful. The present study aims to investigate the possibility of reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets. Fresh platelets will be added to blood samples of treated patients in varying concentrations at specific timepoints to determine the time and amount of fresh platelets needed to normalize platelet reactivity in the treated samples.
Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events, including stent thrombosis, in patients undergoing stent procedures who have not been pretreated with clopidogrel. In vitro investigations have shown cangrelor to be associated with more rapid, potent, and consistent platelet inhibition in patients on maintenance prasugrel therapy exposed to a re-loading dose of prasugrel. However, if cangrelor exerts similar effects in ticagrelor treated patients remain unknown. The aim of the present study is to evaluate the effects on platelet function achieved after in vitro incubation with cangrelor in patients on ticagrelor maintenance dose who receive a loading dose of ticagrelor.
This study involves doing platelet function testing in patients who have undergone fibrinolysis. Fibrinolysis (Use of clot busting medicine in heart attack) is the standard of care to restore blood flow in blocked arteries as soon as possible after the "Heart attack" in rural health center where access to cardiac catheterization is one hour away. Fibrinolysis is done by the emergency room physician in a timely fashion to minimize the damage of the myocardium. Additionally anti-platelet regimen as adjuvant for patient undergoing fibrinolysis has been well studied in many trials. In this study investigators will use clopidogrel or ticagrelor in randomized fashion to evaluate anti- platelet effect by measuring efficacy in vivo (pharmacodynamics) and blood levels of both drugs (Pharmacokinetics).
Recently, two new oral P2Y12 antagonists have been approved for clinical use: prasugrel, a third generation thienopyridine, and ticagrelor, a first in class cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with more potent platelet inhibitory effects compared with clopidogrel. In addition, both agents have shown to be superior to clopidogrel in preventing recurrent ischemic events in the setting of acute coronary syndromes (ACS). Understanding how to switch patients from prasugrel to ticagrelor is an unmet need of clinical interest. The proposed PD investigation will have a prospective, randomized, parallel design aimed to show that switching patients from prasugrel to ticagrelor provides similar levels of platelet inhibition.
This purpose of this study is to measure platelet response to ticagrelor and eptifibatide bolus-only compared with ticagrelor and eptifibatide bolus plus 2-hour infusion administrated after cardiac catheterization in patients undergoing non-emergent percutaneous coronary intervention.
Subjects presenting with probable acute coronary syndromes scheduled for cardiac catheterization will be enrolled in this study. Consented subjects will be randomized to receive ticagrelor started with a loading dose immediately after enrollment versus receiving a loading dose of ticagrelor during cardiac catheterization after diagnostic angiography but prior to stenting. Optical coherence tomography (OCT) will be performed after stenting and the volume of thrombus within the new stent will be measured and compared between the groups.
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.
Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Head-to-head comparisons between the two drugs are lacking.
Recently, two P2Y12 receptor inhibitors have been approved for clinical use: prasugrel and ticagrelor. Both prasugrel and ticagrelor have shown to be associated with more potent antiplatelet effects compared with clopidogrel and are associated with an improved net clinical benefit. However, to date there are limited head-to-head comparisons of these two new agents.
Subjects with acute coronary syndromes scheduled for cardiac catheterization will be enrolled in this study. Subjects that are to be treated clinically with coronary artery stenting will be randomized to receive a loading dose of clopidogrel versus ticagrelor after diagnostic angiography but prior to stenting. Optical coherence tomography (OCT) will be performed after stenting and the presence of blood clots inside the new stent will be measured and compared between the groups.
The purpose of this study is to determine whether treatment with ticagrelor + aspirin is more effective than treatment with clopidogrel + aspirin in patients with type-2 diabetes. Both treatments will be given (separately) to all subjects as a one-time loading dose (i.e. higher than a normal daily dose), followed by daily dose for the next 5 to 7 days. Effectiveness of treatment will be measured with specialized blood tests before the loading dose, at two time-points after the loading dose, and once after the last daily dose.
Antiplatelet therapy remains a cornerstone in the treatment of acute and chronic coronary artery disease. Aspirin was the first such therapy to prove its benefits in acute myocardial infarction. Compared to aspirin monotherapy, the combination of aspirin and clopidogrel, a thienopyridine P2Y12 inhibitor, has been demonstrated to reduce adverse event rates among patients with acute coronary syndromes (with or without ST-segment elevation) and those receiving intracoronary stents. In the Triton-TIMI 38 trial a novel thienopyridine, prasugrel, was compared to clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Although prasugrel significantly reduced recurrent myocardial infarction, bleeding rates were increased and no improvement in cardiac or all-cause mortality was demonstrated. However, in 2009, the authors of the PLATO trial demonstrated an unexpected cardiovascular mortality benefit with ticagrelor over clopidogrel, an endpoint not previously met by any other antiplatelet agent against an active comparator. Based on the reproducible adverse events seen in the DISPERSE, DISPERSE-2, and PLATO trials, an adenosine-mediated effect of ticagrelor is proposed. Hypothesis: The aim of this study is to test the hypothesis that ticagrelor produces pharmacologic ischemic preconditioning, an undescribed potential off-label property of ticagrelor that could represent a plausible mechanism for its effects on cardiovascular mortality.