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

Phase 4

Recruiting

• Conditions: Thrombosis; Myocardial Infarction
• Interventions: Drug: Rivaroxaban; Drug: Ticagrelor

• Registration Number: NCT05116995
• Lead Sponsor: Nova Scotia Health Authority

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)

Study Timeline

• Study First Submitted: 2021-10-21
• Study Start: 2021-11-01
• Study First Submitted QC: 2021-11-02
• Study First Posted: 2021-11-11
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-21
• Last Update Posted: 2023-09-22
• Primary Completion: 2023-11-01
• Study Completion: 2023-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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:

  1. Diffuse coronary artery disease.
  2. Peripheral vascular disease
  3. Diabetes
  4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Rivaroxaban first	Rivaroxaban	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.
Rivaroxaban first	Ticagrelor	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.
Ticagrelor first	Rivaroxaban	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.
Ticagrelor first	Ticagrelor	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.

Primary Outcome Measures

Name	Time	Method
Bleeding time	7 days	The primary objective is to determine the differential effect of rivaroxaban and ticagrelor on bleeding time as a surrogate marker for bleeding tendency.

Secondary Outcome Measures

Name	Time	Method
Differential effects on inflammatory markers (white cell count and CRP)	7 days	These will be measured from blood draws
Differential effects on fibrin clot lysis time	7 days	This will be measured from blood draws

Trial Locations

Locations (1)

Nova Scotia Health; 🇨🇦 Halifax, Nova Scotia, Canada