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

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT02287909
• Collaborator: (none)
• Enrollment: 87
• Location: 1
• Arms: 4
• Actual Duration (Months): 39
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Clopidogrel; Drug: Ticagrelor	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacodynamic Evaluation of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A) clopidogrel 600 mg LD 24 hours after last MD of ticagrelor 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; Swiching from ticagrelor to clopidogrel; Other Names: Plavix
Experimental: B) clopidogrel 600 mg LD 12 hours after last MD of ticagrelor 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; Swiching from ticagrelor to clopidogrel; Other Names: Plavix
Experimental: C) clopidogrel 75mg MD 24 hours after last MD of ticagrelor 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; Swiching from ticagrelor to clopidogrel; Other Names: Plavix
Active Comparator: D) continue ticagrelor MD 90mg twice daily 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; Continue treatment with ticagrelor; Other Names: Brilinta

Outcome Measures

Primary Outcome Measures

1. Platelet Reactivity Unit [48 hours after switch]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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].

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Jacksonville	Florida	United States	32209

Sponsors and Collaborators

• University of Florida

Investigators

• Principal Investigator: Dominick Angiolillo, University of Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 21, 2017

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02287909
• Other Study ID Numbers: UFJ 2014-153
• First Posted: Nov 11, 2014
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Pre-assignment Detail	87 patients entered a run-in phase. Of these, 7 withdrew during run in.

Arm/Group Title	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	D) Continue Ticagrelor MD 90mg Twice Daily
Arm/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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Ticagrelor: Continue treatment with ticagrelor
Period Title: Overall Study
STARTED	20	20	20	20
COMPLETED	18	19	20	19
NOT COMPLETED	2	1	0	1

Baseline Characteristics

Arm/Group Title	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	D) Continue Ticagrelor MD 90mg Twice Daily	Total
Arm/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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Ticagrelor: Continue treatment with ticagrelor	Total of all reporting groups
Overall Participants	20	20	20	20	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (7)	65 (8)	63 (9)	58 (9)	62 (8)
Sex: Female, Male (Count of Participants)
Female	9 45%	5 25%	7 35%	8 40%	29 36.3%
Male	11 55%	15 75%	13 65%	12 60%	51 63.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	10 50%	5 25%	7 35%	6 30%	28 35%
White	10 50%	14 70%	13 65%	14 70%	51 63.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5%	0 0%	0 0%	1 1.3%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	20 100%	20 100%	20 25%

Outcome Measures

1. Primary Outcome

Title	Platelet Reactivity Unit
Description	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
Time Frame	48 hours after switch

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	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	D) Continue Ticagrelor MD 90mg Twice Daily
Arm/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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Clopidogrel: Swiching from ticagrelor to clopidogrel	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 Ticagrelor: Continue treatment with ticagrelor
Measure Participants	18	19	20	19
Least Squares Mean (Standard Error) [PRU]	177 (27)	164 (24)	174 (24)	26 (25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A) Clopidogrel 600 mg LD 24 Hours After Last MD of Ticagrelor, C) Clopidogrel 75mg MD 24 Hours After Last MD of Ticagrelor
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) 985%; -38 to 24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	10 days
Arm/Group Title	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		D) Continue Ticagrelor MD 90mg Twice Daily
Arm/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 Clopidogrel: Swiching from ticagrelor to clopidogrel		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 Clopidogrel: Swiching from ticagrelor to clopidogrel		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 Clopidogrel: Swiching from ticagrelor to clopidogrel		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 Ticagrelor: Continue treatment with ticagrelor
All Cause Mortality
	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		D) Continue Ticagrelor MD 90mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	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		D) Continue Ticagrelor MD 90mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	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		D) Continue Ticagrelor MD 90mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/20 (0%)		0/20 (0%)		2/20 (10%)
Respiratory, thoracic and mediastinal disorders
Dypnea	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1
Vascular disorders
Bleeding	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.