Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease (SWAP-4)

University of Florida

Status and phase: Completed; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Clopidogrel; Drug: Ticagrelor

Study type: Interventional

Funder types: Other

Identifiers

NCT02287909

UFJ 2014-153

Details and patient eligibility

About

The recommended antiplatelet treatment regimen for patients affected by acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) consists in the combination of aspirin and a P2Y12 receptor inhibitor. More potent P2Y12 receptor inhibitors, such as ticagrelor, have been developed which are associated with less response variability than clopidogrel and better clinical outcomes. Ticagrelor use has increased significantly because of its more expanded Food and Drug Administration (FDA) indications compared with prasugrel. However, despite the evidence for sustained efficacy and safety, many physicians limit treatment duration with ticagrelor to the early phases following an ACS mostly due to cost issues and concerns about increased bleeding. Therefore, it is very common in clinical practice to switch patients while on maintenance dosing (MD) with ticagrelor to treatment with clopidogrel. However, the pharmacodynamic (PD) effects of switching from ticagrelor to clopidogrel remain unknown. Therefore, the aim of this investigation is to evaluate the PD effects of switching from ticagrelor to clopidogrel.

Full description

The recommended antiplatelet treatment regimen for patients affected by acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) consists in the combination of aspirin and a P2Y12 receptor inhibitor. Currently, three P2Y12 receptor inhibitors are available for clinical use (clopidogrel, prasugrel, and ticagrelor). Among these, clopidogrel remains the most widely used. However, recent studies have shown that there is a broad variability in platelet-inhibitory response induced by clopidogrel, which in turn is associated with worse outcomes. More potent P2Y12 receptor inhibitors (prasugrel and ticagrelor) have been developed which are associated with less response variability than clopidogrel and better clinical outcomes. Ticagrelor use has increased significantly because of its more expanded Food and Drug Administration (FDA) indications compared with prasugrel. However, despite the evidence for sustained efficacy and safety, many physicians limit treatment duration with ticagrelor to the early phases following an ACS (early weeks or months, rather than one-year) mostly due to cost issues and concerns about increased bleeding. Therefore, it is very common in clinical practice to switch patients while on maintenance dosing (MD) with ticagrelor to treatment with clopidogrel. However, the pharmacodynamic (PD) effects of switching from ticagrelor to clopidogrel remain unknown. In addition, it is unknown whether switching from ticagrelor to clopidogrel should occur with or without a loading dose (LD). Therefore, the aim of this investigation is to evaluate the PD effects of switching from ticagrelor to clopidogrel with and without a LD. The present study has a prospective, randomized, open-label design, in which patients will be treated with 4 different strategies to assess PD profiling after switching. This study will provide important insights on PD effects of switching from ticagrelor to clopidogrel.

Enrollment: 87 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Patients with angiographically documented CAD
2. On therapy with aspirin(<100mg/day) and clopidogrel (75mg/day) for at least 30 days per standard of care
3. Age between 18 and 80 years old

Exclusion Criteria

1. History of intracranial bleeding
2. Severe hepatic impairment (ALT >2.5 times the upper limit of normal)
3. Active bleeding or propensity to bleed or blood dycrasia
4. Platelet count <80x106/mL
5. Hemoglobin <10g/dL
6. Hemodynamic instability
7. Estimated glomerular filtration rate (eGFR) <30 mL/min
8. On treatment with oral anticoagulants
9. Patients with sick sinus syndrome (SSS) or II or III degree AV block without pacemaker protection
10. Drugs interfering CYP3A4 metabolism (to avoid interaction with ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromizycin
11. Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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87 participants in 4 patient groups

A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor

Experimental group

Description:

Patients will be randomized (1:1:1:1) into one of the four following groups: A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor, followed by 75mg daily MD; B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor, followed by 75mg daily MD; C) clopidogrel 75mg daily MD 24 hours after last MD of ticagrelor; D) continue ticagrelor MD 90mg twice daily

Treatment:

Drug: Clopidogrel

B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor

Experimental group

Description:

Patients will be randomized (1:1:1:1) into one of the four following groups: A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor, followed by 75mg daily MD; B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor, followed by 75mg daily MD; C) clopidogrel 75mg daily MD 24 hours after last MD of ticagrelor; D) continue ticagrelor MD 90mg twice daily

Treatment:

Drug: Clopidogrel

C) clopidogrel 75mg MD 24 hours after last MD of ticagrelor

Experimental group

Description:

Patients will be randomized (1:1:1:1) into one of the four following groups: A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor, followed by 75mg daily MD; B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor, followed by 75mg daily MD; C) clopidogrel 75mg daily MD 24 hours after last MD of ticagrelor; D) continue ticagrelor MD 90mg twice daily

Treatment:

Drug: Clopidogrel

D) continue ticagrelor MD 90mg twice daily

Active Comparator group

Description:

Patients will be randomized (1:1:1:1) into one of the four following groups: A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor, followed by 75mg daily MD; B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor, followed by 75mg daily MD; C) clopidogrel 75mg daily MD 24 hours after last MD of ticagrelor; D) continue ticagrelor MD 90mg twice daily

Treatment:

Drug: Ticagrelor