A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders - Study Results

A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders (RESPOND)

This study has been completed.

Study NCT00642811 Information provided by AstraZeneca

First Received on March 19, 2008. Last Updated on August 30, 2011 History of Changes

Results First Received: January 27, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Pharmacodynamics Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Stable Coronary Artery Disease
Interventions:	Drug: Ticagrelor Drug: Clopidogrel Drug: Aspirin

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; switch to ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks.
Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; switch to clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks.
Clopidogrel Responders - Clopidogrel to Clopidogrel	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; stay on clopidogrel 75 mg once daily (od) for 2 weeks
Clopidogrel Responders - Clopidogrel to Ticagrelor	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; switch to ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks.
Clopidogrel Responders - Ticagrelor to Clopidogrel	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; switch to clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks.
Clopidogrel Responders - Ticagrelor to Ticagrelor	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; stay on ticagrelor 90 mg twice daily (bd) for 2 weeks.

Participant Flow: Overall Study

	Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Clopidogrel to Clopidogrel	Clopidogrel Responders - Clopidogrel to Ticagrelor	Clopidogrel Responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Ticagrelor to Ticagrelor
STARTED	20	21	13	16	14	14
COMPLETED	17	17	13	15	13	13
NOT COMPLETED	3	4	0	1	1	1
Adverse Event	2	3	0	0	0	1
Developement of discontinuation criteria	0	0	0	0	1	0
Severe Non-compliance to protocol	1	0	0	0	0	0
Other	0	1	0	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Clopidogrel Responders - Clopidogrel to Clopidogrel	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Clopidogrel Responders - Clopidogrel to Ticagrelor	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Clopidogrel Responders - Ticagrelor to Clopidogrel	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Clopidogrel Responders - Ticagrelor to Ticagrelor	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist

Baseline Measures

	Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Clopidogrel to Clopidogrel	Clopidogrel Responders - Clopidogrel to Ticagrelor	Clopidogrel Responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Ticagrelor to Ticagrelor	Total
Number of Participants [units: participants]	20	21	13	16	14	14	98
Age [units: year] Mean ± Standard Deviation	67.25 ± 8.12	64.57 ± 6.31	65.46 ± 8.68	64.56 ± 8.56	63.21 ± 9.23	61.57 ± 8.22	64.8 ± 7.95
Gender [units: Participants]
Female	5	8	3	2	3	1	22
Male	15	13	10	14	11	13	76

Outcome Measures

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1. Primary:

Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.) [ Time Frame: Day 14 and Day 28, 4 Hrs Post Dose. ]

Show Outcome Measure 1

2. Primary:

Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop. [ Time Frame: Day 14, and day 28, 4 hours post dose ]

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3. Secondary:

Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 [ Time Frame: Day 15, 4 hrs post switching ]

Show Outcome Measure 3

4. Secondary:

Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28 [ Time Frame: 4 hrs post first dose on day 28 ]

Show Outcome Measure 4

5. Secondary:

Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 [ Time Frame: Day 15, 4 hrs post switching ]

Show Outcome Measure 5

6. Secondary:

Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28 [ Time Frame: 4 hrs post first dose on day 28 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: An Investigator agrees to provide a copy of the publication to AZ for review at least 60 days in advance of submission for publication. Investigators in multicenter (MC) studies agree to postpone MC publications until the earlier of the date of the first AZ-authorized MC publication or a period up to 18 months from study completion at all sites.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com

No publications provided by AstraZeneca

Publications automatically indexed to this study:

Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec 1;3(6):556-66. Epub 2010 Nov 15.

Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. Epub 2010 Mar 1.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00642811 History of Changes
Other Study ID Numbers:	D5130C00030
Study First Received:	March 19, 2008
Results First Received:	January 27, 2011
Last Updated:	August 30, 2011
Health Authority:	United States: Food and Drug Administration