Study To Evaluate Cardiac Assessments Following Different Treatments Of Smoking Cessation Medications In Subjects With And Without Psychiatric Disorders. (CATS)

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label)
Condition:	Smoking Cessation
Interventions:	Drug: placebo; Drug: varenicline tartrate; Drug: bupropion hydrochloride; Drug: Nicotine Replacement Therapy Patch

  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
Of the 6293 participants who completed the parent study NCT01456936 as per protocol, a total of 4595 participants enrolled into this study NCT01574703 from 132 centers in 16 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This is a non-treatment extension study of parent study NCT01456936. No study drug was provided in this extension phase. However, cardiovascular events that occurred during parent study NCT01456936 when participants received varenicline(N=2016), bupropion(N=2006),NRT(N=2022), or placebo(N=2014) in a triple-dummy design were analyzed in this study.

Reporting Groups

	Description
Varenicline	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received varenicline in a triple-dummy design were analyzed as part of this study.
Bupropion	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received bupropion in a triple-dummy design were analyzed as part of this study.
Nicotine Replacement Therapy (NRT) Patch	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received NRT patch in a triple-dummy design were analyzed as part of this study.
Placebo	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received placebo in a triple-dummy design were analyzed as part of this study.

Participant Flow:   Overall Study

	Varenicline	Bupropion	Nicotine Replacement Therapy (NRT) Patch	Placebo
STARTED	1192	1166	1116	1121
COMPLETED	1067	1054	1011	1007
NOT COMPLETED	125	112	105	114
Adverse Event	0	2	1	1
Protocol Violation	0	0	0	1
Unspecified Reason	27	15	20	16
Withdrawal by Subject	53	52	36	61
Met Withdrawal Criteria	0	1	1	0
Lost to Follow-up	43	41	46	35
Death	2	1	1	0

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The term Baseline visit refers to the Baseline (Week 0) visit of the parent study NCT01456936. The safety population included all participants who received at least one dose of study drug in NCT01456936 parent study. The below Baseline characteristics (age, gender) are presented for all participants who entered study NCT01574703.

Reporting Groups

	Description
Varenicline	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received varenicline in a triple-dummy design were analyzed as part of this study.
Bupropion	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received bupropion in a triple-dummy design were analyzed as part of this study.
NRT Patch	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received NRT patch in a triple-dummy design were analyzed as part of this study.
Placebo	This was the non-treatment extension study of parent study NCT01456936. No study drug was provided during this extension phase. However, Cardiovascular events that occurred during parent study NCT01456936 when participants received placebo in a triple-dummy design were analyzed as part of this study.
Total	Total of all reporting groups

Baseline Measures

	Varenicline	Bupropion	NRT Patch	Placebo	Total
Overall Participants Analyzed; [Units: Participants]	1192	1166	1116	1121	4595
Age; [Units: Years]; Mean (Standard Deviation)	48.1 (12.2)	47.7 (12.5)	48.3 (11.9)	47.5 (12.2)	47.9 (12.2)
Gender; [Units: Participants]; Count of Participants
Female	659 55.3%	648 55.6%	623 55.8%	621 55.4%	2551 55.5%
Male	533 44.7%	518 44.4%	493 44.2%	500 44.6%	2044 44.5%

  Outcome Measures

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1. Primary:

Time to Occurrence of Major Adverse Cardiovascular Event (MACE) During Treatment Period (up to Date of Last Dose of Study Drug) in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks). ]

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2. Secondary:

Time to MACE up to Date of Last Dose of Study Drug Plus 30 Days Follow-up in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks) plus 30 days. ]

  Show Outcome Measure 2

3. Secondary:

Time to MACE Until the End of Study NCT01574703. [ Time Frame: Baseline until end of study (end of study is defined as last visit in study NCT01574703 [up to Week 52], or in study NCT01456936 [up to 24 Weeks] for those participants not enrolled into study NCT01574703). ]

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4. Secondary:

Incidence of MACE Assessed During Treatment Period (up to Date of Last Dose of Study Drug) in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks). ]

  Show Outcome Measure 4

5. Secondary:

Incidence of MACE + Assessed During Treatment Period (up to Date of Last Dose of Study Drug) in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks). ]

  Show Outcome Measure 5

6. Secondary:

Incidence of MACE Assessed up to Date of Last Dose of Study Drug Plus 30 Days Follow-up in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks) plus 30 days follow-up. ]

  Show Outcome Measure 6

7. Secondary:

Incidence of MACE+ Assessed up to Date of Last Dose of Study Drug Plus 30 Days Follow-up in Study NCT01456936. [ Time Frame: Baseline to last dose of study drug in parent study NCT01456936 (up to 12 weeks) plus 30 days follow-up. ]

  Show Outcome Measure 7

8. Secondary:

Incidence of MACE Assessed Until End of Study NCT01574703. [ Time Frame: Baseline until end of study (end of study is defined as last visit in study NCT01574703 [up to Week 52], or in study NCT01456936 [up to 24 Weeks] for those participants not enrolled into study NCT01574703). ]

  Show Outcome Measure 8

9. Secondary:

Incidence of MACE+ Assessed Until End of Study NCT01574703. [ Time Frame: Baseline until end of study (end of study is defined as last visit in study NCT01574703 [up to Week 52], or in study NCT01456936 [up to 24 Weeks] for those participants not enrolled into study NCT01574703). ]

  Show Outcome Measure 9

  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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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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  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: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact:  

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Benowitz NL, Pipe A, West R, Hays JT, Tonstad S, McRae T, Lawrence D, St Aubin L, Anthenelli RM. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):622-631. doi: 10.1001/jamainternmed.2018.0397.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01574703 History of Changes
Other Study ID Numbers:	A3051148; 2011-005513-37 ( EudraCT Number ); CATS ( Other Identifier: Alias Study Number )
First Submitted:	April 6, 2012
First Posted:	April 10, 2012
Results First Submitted:	July 7, 2016
Results First Posted:	December 29, 2016
Last Update Posted:	December 29, 2016