Cohort Study of Pioglitazone and Bladder Cancer in Patients With Type II Diabetes

Tracking Information
First Submitted Date	July 7, 2012
First Posted Date	July 11, 2012
Results First Submitted Date	August 31, 2012
Results First Posted Date	October 12, 2012
Last Update Posted Date	March 7, 2018
Study Start Date	July 2004
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: December 9, 2015)	Incident Diagnosis of Bladder Cancer (10-year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ]; Incident bladder cancers were identified from January 1, 1997 to December 31, 2012.
Original Primary Outcome Measures; (submitted: July 7, 2012)	Number of Participants With Newly Diagnosed Bladder Cancer [ Time Frame: January 1, 1997 to December 31, 2010. ]Bladder cancers were identified from the KPNC cancer registry from January 1, 1997 to December 31, 2010. This was supplemented by case identification through surveillance of electronic pathology reports within KPNC for the period from January 1, 2005 to December 31, 2010.; Incident Diagnosis of Bladder Cancer [ Time Frame: January 1, 1997 to December 31, 2010. ]Incident bladder cancers were identified from the KPNC cancer registry from January 1, 1997 to December 31, 2010. This was supplemented by case identification through surveillance of electronic pathology reports within KPNC for the period from January 1, 2005 to December 31, 2010. Incidence is reported as the number of newly diagnosed cases of bladder cancer per 100,000 person years. The 95% confidence interval was calculated using the Poisson method.
Change History	Complete list of historical versions of study NCT01637935 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: December 9, 2015)	Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ]; Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ]; Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ]; Stage of Bladder Cancer (10 Year Analysis) [ Time Frame: January 1, 1997 to December 31, 2012 ]
Original Secondary Outcome Measures	Not Provided
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Cohort Study of Pioglitazone and Bladder Cancer in Patients With Type II Diabetes
Official Title	Cohort Study of Pioglitazone and Bladder Cancer in Patients With Diabetes
Brief Summary	To assess the potential association between pioglitazone and bladder cancer compared with non-pioglitazone users among patients with type 2 diabetes mellitus.
Detailed Description	Following guidance from the United States Food and Drug Administration (FDA) and European Medicines Agency, the University of Pennsylvania and Kaiser Permanente Northern California (KPNC) designed and conducted this study using the KPNC database to assess the potential association between pioglitazone and bladder cancer among patients with type 2 diabetes mellitus. The study was conducted over the course of 10 years, with a series of interim analyses undertaken during this period and provided to the sponsor (Takeda) and the appropriate regulatory agencies. In 2011, the planned 5-year interim analysis of this study was published in Diabetes Care. That report included data from 1 January 1997 to 30 April 2008. Following reporting of these data, there was a request from the FDA for an additional fourth interim analysis at 8 years including data from 1 January 1997 to 31 December 2010. In August 2011 the FDA requested inclusion of a sensitivity analysis to assess change of cohort entry criteria to minimize left censoring of exposure. Included in the FDA request was a duration analysis for other antidiabetic medications. In August 2014, the final 10-year analyses were completed and submitted to the sponsor and regulatory agencies. Interim results previously posted on clinicaltrials.gov are available in the public archive
Study Type	Observational
Study Design	Observational Model: Cohort; Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
Sampling Method	Probability Sample
Study Population	The study was conducted within Kaiser Permanente Northern California (KPNC), which provides comprehensive healthcare services to approximately 3.2 million members. The source population was identified from the KPNC diabetes registry, which was first constructed in 1993 and has been updated annually since then. The registry identifies patients primarily from four data sources: primary hospital discharge diagnoses of diabetes mellitus (since 1971); two or more outpatient visit diagnoses of diabetes (since 1995); any prescription for a diabetes-related medication (since 1994); or any record of an abnormal hemoglobin A1c (HbA1c) test (>6.7%) (since 1991). The diabetes registry gathers data from a variety of KPNC electronic medical records (EMR) to build and follow the registry cohort across time. These data include cancer registries, pharmacy records, laboratory records, and inpatient and outpatient medical diagnoses.
Condition	Diabetes; Bladder Cancer
Intervention	Drug: Pioglitazone; Pioglitazone tablets.; Other Name: Actos
Study Groups/Cohorts	Pioglitazone exposed group Defined as those patients having filled at least two prescriptions for pioglitazone within a 6-month period. Patients in the pioglitazone group may also have exposure to other diabetic medications Intervention: Drug: Pioglitazone; Pioglitazone unexposed group Defined as patients who did not fill at least two prescriptions for pioglitazone within a 6-month period. Patients in the pioglitazone unexposed group may have been exposed to other diabetic medications. This group also included diabetic patients without any diabetic medications.
Publications *	Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CP Jr, Vaughn DJ, Nessel L, Selby J, Strom BL. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011 Apr;34(4):916-22. doi: 10.2337/dc10-1068.; Lewis JD, Habel LA, Quesenberry CP, Strom BL, Peng T, Hedderson MM, Ehrlich SF, Mamtani R, Bilker W, Vaughn DJ, Nessel L, Van Den Eeden SK, Ferrara A. Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. JAMA. 2015 Jul 21;314(3):265-77. doi: 10.1001/jama.2015.7996.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Actual Enrollment; (submitted: July 7, 2012)	193099
Original Actual Enrollment	Same as current
Actual Study Completion Date	August 2014
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria	Inclusion Criteria: The study cohort included both patients with an established diagnosis of diabetes mellitus prior to January 1, 1997 and those who were newly diagnosed prior to December 31, 2002. Patients were eligible for the study cohort if they met any of the following criteria: As of January 1, 1997 they had been diagnosed with diabetes mellitus, were age 40 or older and were members of KPNC, They had been diagnosed with diabetes mellitus, reached age 40 between January 1, 1997 and December 31, 2002 and were KPNC members on their 40th birthday, or Had diabetes mellitus and were age 40 or older when they joined KPNC between January 1, 1997 and December 31, 2002. Exclusion Criteria:; Diagnosis of bladder cancer recorded in the KPNC cancer registry prior to entry to the cohort or within 6 months of entry into KPNC.
Sex/Gender	Sexes Eligible for Study: All
Ages	40 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	Not Provided
Removed Location Countries
Administrative Information
NCT Number	NCT01637935
Other Study ID Numbers	01-03-TL-OPI-524; U1111-1132-3482 ( Registry Identifier: WHO )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Takeda
Study Sponsor	Takeda
Collaborators	Kaiser Permanente; Department of Epidemiology at University of Pennsylvania
Investigators	Not Provided
PRS Account	Takeda
Verification Date	February 2018