CAPITAL PCI AF: The Safety and Efficacy Of Rivaroxaban and Ticagrelor for Patients With Atrial Fibrillation After Percutaneous Coronary Intervention

Sponsor

Ottawa Heart Institute Research Corporation (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03331484

Collaborator

(none)

Enrollment

Location

Arm

49.4

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Currently, there is minimal data on the combination of rivaroxaban and ticagrelor in patients with atrial fibrillation (AF) managed with percutaneous coronary intervention (PCI). Furthermore, there exists significant controversy among physicians in the use of oral anticoagulants in conjunction with antiplatelet therapy in this population. The present recommendation is triple therapy (aspirin + clopidogrel + warfarin), which has been related to major bleeding complications. Previous studies have shown that ticagrelor has been proven to be more effective in reducing the rate of death, new heart attacks, or strokes than the previously recommended drug, clopidogrel, and studies have shown that less bleeding occurs with rivaroxaban than with warfarin. Therefore, it would be ideal to investigate the two potent drugs, ticagrelor and rivaroxaban, in combination in order to gain insight in the management of these high-risk patients.

The CAPITAL PCI AF study is a phase 3 Health Canada regulated interventional study involving the use of investigational drugs. It is a non-randomized, open-design study. The investigational team is studying the highly potent drug Ticagrelor, which is prescribed to participants receiving a stent placement, given in combination with Rivaroxaban, an oral anticoagulant recommended for patients with AF. The primary clinical endpoint is a safety outcome measuring bleeding complications in participants with AF treated within one year of the index PCI. The primary efficacy endpoint is measured by the clinical outcomes of death, stroke, non-central nervous system systemic embolism, myocardial infarction, and stent thrombosis within one year of the index PCI.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Acute Coronary Syndrome	Drug: Ticagrelor Drug: Rivaroxaban	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

THE CAPITAL PCI AF Study: The Safety and Efficacy of Rivaroxaban and Ticagrelor for Patients With Atrial Fibrillation After Percutaneous Coronary Intervention

Actual Study Start Date :

Nov 1, 2018

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Dec 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Ticagrelor and Rivaroxaban All participants will be prescribed ticagrelor 90 mg twice daily and rivaroxaban 15 mg once daily for a year.	Drug: Ticagrelor Ticagrelor 90 mg twice daily Drug: Rivaroxaban Rivaroxaban 15 mg once daily (10mg for patients with moderate renal impairment, creatinine clearance: 30-50 mL/min by the Cockcoft Gault method)

Arm

Intervention/Treatment

Other: Ticagrelor and Rivaroxaban

All participants will be prescribed ticagrelor 90 mg twice daily and rivaroxaban 15 mg once daily for a year.

Drug: Ticagrelor

Ticagrelor 90 mg twice daily

Drug: Rivaroxaban

Rivaroxaban 15 mg once daily (10mg for patients with moderate renal impairment, creatinine clearance: 30-50 mL/min by the Cockcoft Gault method)

Outcome Measures

Primary Outcome Measures

Composite of TIMI Bleeds [12 months]
Composite of TIMI Major Bleed, Minor Bleed, and Bleeding requiring medical attention

Secondary Outcome Measures

The frequency of the individual components of the primary endpoint [12 months]
Frequency of TIMI major, TIMI Minor, and TIMI bleeding requiring medical attention
The composite of multiple adverse cardiovascular events (MACE) [12 months]
The composite of cardiovascular death and stroke events and its individual components
The frequency of stent thrombosis [12 months]
All-cause mortality [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient has undergone a PCI with stent placement, plus
Documented non-valvular atrial fibrillation (AF)* within 1 year before screening, OR

1 year before screening if patient had been receiving oral anticoagulation (OAC)therapy for the atrial fibrillation for 3 months immediately before the index PCI.

AF is defined by its presence on an electrocardiogram (ECG), Holter monitor, or any device that provides a rhythm strip documenting paroxysmal, persistent or, permanent atrial fibrillation.

Atrial flutter can be included as "AF equivalent". The stroke risk in patients with atrial flutter is not much different from that in AF. Furthermore, many patients diagnosed with atrial flutter subsequently develop AF. Hence, current guidelines recommend that OAC should be used in patients with atrial flutter similar to that in patients with AF.

Non-valvular AF is defined as the absence of moderate to severe mitral stenosis or the presence of a mechanical valve as per 2016 ESC guidelines.

Exclusion Criteria:

Age <18 years old
Any condition that contraindicates anticoagulant therapy or would confer an unacceptable risk of bleeding, such as, but not limited to:

active internal bleeding, ii. bleeding at a non-compressible site, iii. bleeding diathesis within 30 days of PCI, iv. baseline platelet count <90,000/μL, v. history of intracranial hemorrhage, vi. clinically significant gastrointestinal bleeding within 12 months of PCI, vii. baseline INR > 1.5 in patients not prescribed VKA, suggesting underlying coagulation disorder.

History of stroke
Cardiogenic shock at the time of screening
Ventricular arrhythmias refractory to treatment at the time of screening
Calculated CrCl <30 mL/min at the time of screening
Known significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis), or liver function test (LFT) abnormalities at screening: alanine transaminase (ALT) >5 times the upper limit of normal or ALT >3 times the upper limit of normal plus total bilirubin >2 times the upper limit of normal
Hemoglobin level <90 g/dL at screening
Any severe condition that would limit life expectancy to less than 12 months
Major surgery, biopsy of a parenchymal organ, or serious trauma within the past 30 days
Incomplete staged PCI procedure (once completion of the staged PCI has occurred, the final PCI may become the index event)
CABG planned
Transient AF caused by a reversible disorder (e.g. thyrotoxicosis, pulmonary embolism, recent surgery)
Any condition other than non-valvular AF requiring long-term anticoagulation with VKAs such as moderate to severe mitral valve stenosis, mechanical heart valves, deep vein thrombosis, pulmonary embolism, or left ventricular thrombus
Known allergies, hypersensitivity, or intolerance to rivaroxaban or ticagrelor
Pregnant or planning to become pregnant while enrolled in this study, or unwilling to employ an investigator-approved method of birth control
Participation in a study with another investigational device or drug < four weeks
Is receiving systemic treatment with strong inhibitors of both cytochrome P450 (CYP) 3A4 and p-glycoprotein (P-gp; eg, the azole-antimycotic ketoconazole and the HIV-protease inhibitor ritonavir). Treatment with fluconazole is allowed.
CHADS-VASC <1