Differential EFfects of Dual antIplatelet and Dual aNtithrombotic thErapy on Hemostasis in Chronic Coronary Syndrome Patients

Study Overview
=================
Brief Summary
-----------------
The investigators will be comparing the effects of two different drug treatment strategies, in patients with history of a heart attack, on different markers of bleeding and clotting risk. Both treatment strategies are already approved for the indication of improving outcomes in high-risk patients with history of heart attack.

Detailed Description
-----------------
The investigators will enroll patients with coronary disease >1 year after an acute coronary syndrome. Subjects will be randomized to one of two treatment plans. One plan the participant will take ticagrelor for one week, then take two weeks off with no drug (washout period), then one week of rivaroxaban. The other plan will be reverse order where the participant will take rivaroxaban for one week, then two weeks off(washout period), then one week of ticagrelor. Study drugs will be provided to participants at the start of each treatment period. Bleeding time will be determined and blood samples will be taken at four timepoints (baseline, post first drug, pre second drug, and post second drug) to measure complete blood count, CRP, and fibrin clot assessment. These are surrogate markers for safety (bleeding) and efficacy (increased thrombotic risk)

Official Title
-----------------
Differential EFfects of Dual antIplatelet and Dual aNtithrombotic thErapy on Hemostasis in Chronic Coronary Syndrome Patients: Define CCS Study, a Prospective Randomized Crossover Clinical Trial.

Conditions
-----------------
Thrombosis, Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Rivaroxaban
* Drug: Ticagrelor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with chronic coronary syndrome (at least 1 year after having a myocardial infarction) on aspirin monotherapy will be eligible for this study. They have to have at least one of these additional risk factors: Diffuse coronary artery disease. Peripheral vascular disease Diabetes Chronic kidney disease (eGFR<60 ml/unit/1.73 m2) Exclusion Criteria: Allergy to either rivaroxaban or ticagrelor Requirement for anticoagulation or P2Y12 inhibitor therapy Anemia (hemoglobin < 10 g/dL) Severe renal impairment (eGFR < 30 ml/unit/1.73 m2) Bleeding disorders Significant liver impairment resulting in deranged clotting parameters Any history of intracranial hemorrhage Stroke within 6 months History of gastrointestinal bleed within 6 months Major surgery within 1 month Patients with inflammatory conditions Concomitant treatment with immunosuppressive therapy, inhibitors or inducers of P glycoprotein or CYP3A4 enzymes (eg. azole antifungals, ritonavir, erythromycin, clarithromycin, rifampicin) Concomitant treatment with antidepressants (selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors) Pregnancy Inability to give written consent

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Treatment #1 for one week then on Day 21 they enter Treatment #2 for 1 week.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rivaroxaban first<br>Patients will be treated with rivaroxaban 2.5 mg twice a day for one week then on Day 21, will be treated with ticagrelor 60 mg twice a day for one week. | Drug: Rivaroxaban<br>* rivaroxaban 2.5 mg twice a day for 7 days<br>* Other names: xarelto;Drug: Ticagrelor<br>* Ticagrelor 60 mg twice a day for 7 days<br>* Other names: brilinta;|
| Active Comparator: Ticagrelor first<br>Patients will be treated with ticagrelor 60 mg twice a day for one week then on Day 21, will be treated with rivaroxaban 2.5 mg twice a day for one week. | Drug: Rivaroxaban<br>* rivaroxaban 2.5 mg twice a day for 7 days<br>* Other names: xarelto;Drug: Ticagrelor<br>* Ticagrelor 60 mg twice a day for 7 days<br>* Other names: brilinta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding time | The primary objective is to determine the differential effect of rivaroxaban and ticagrelor on bleeding time as a surrogate marker for bleeding tendency. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differential effects on inflammatory markers (white cell count and CRP) | These will be measured from blood draws | 7 days | 
| Differential effects on fibrin clot lysis time | This will be measured from blood draws | 7 days |