Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease

NCT02287909 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: UFJ 2014-153
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity Unit

  PRU assessed by VerifyNow at 48 hours after switching of clopidogrel 600 mg LD administered 24 hours after the last ticagrelor MD vs. clopidogrel 75 mg MD given 24 hours after the last ticagrelor MD

  48 hours after switch

Study Arms (4)

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

EXPERIMENTAL

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

Drug: Clopidogrel

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

EXPERIMENTAL

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

Drug: Clopidogrel

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

EXPERIMENTAL

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

Drug: Clopidogrel

D) continue ticagrelor MD 90mg twice daily

ACTIVE COMPARATOR

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

Drug: Ticagrelor

Interventions

Clopidogrel DRUG

Swiching from ticagrelor to clopidogrel

Also known as: Plavix

A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor; B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor; C) clopidogrel 75mg MD 24 hours after last MD of ticagrelor

Ticagrelor DRUG

Continue treatment with ticagrelor

Also known as: Brilinta

D) continue ticagrelor MD 90mg twice daily

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Franchi F, Rollini F, Rivas Rios J, Rivas A, Agarwal M, Kureti M, Nagaraju D, Wali M, Shaikh Z, Briceno M, Nawaz A, Moon JY, Been L, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study. Circulation. 2018 Jun 5;137(23):2450-2462. doi: 10.1161/CIRCULATIONAHA.118.033983. Epub 2018 Mar 11.

  PMID: 29526833 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dominick J. Angiolillo, MD, PhD
• Organization: University of Florida

dominick.angiolillo@jax.ufl.edu

9042443378

Study Officials

• Dominick Angiolillo

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 11, 2014
• Study Start: December 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: March 1, 2018
• Last Updated: September 16, 2020
• Results First Posted: August 21, 2020

Record last verified: 2020-08

Locations

US (1)