Differential EFfects of Dual antIplatelet and Dual aNtithrombotic thErapy on Hemostasis in Chronic Coronary Syndrome Patients (DEFINE CCS)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Ticagrelor

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wael Sumaya, PhD; Phone Number: 9024735769; Email: wael.sumaya@nshealth.ca
• Study Contact Backup: Name: David M Fillmore, BSc; Phone Number: 9024737417; Email: david.fillmore@nshealth.ca

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Recruiting
      • Nova Scotia Health
      • Contact: David M Fillmore, BSc; Phone Number: 902-473-7417

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rivaroxaban first; 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; rivaroxaban 2.5 mg twice a day for 7 days; Other Names: xarelto; Drug: Ticagrelor; Ticagrelor 60 mg twice a day for 7 days; Other Names: brilinta
Active Comparator: Ticagrelor first; 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; rivaroxaban 2.5 mg twice a day for 7 days; Other Names: xarelto; Drug: Ticagrelor; Ticagrelor 60 mg twice a day for 7 days; 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

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): November 1, 2023

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Myocardial Infarction; Infarction; Thrombosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Ticagrelor; Rivaroxaban
• Other Study ID Numbers: SUM001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No