Clinical trial NCT01637935: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes
Bladder Cancer
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Kaiser Permanente
name: Department of Epidemiology at University of Pennsylvania
First posted: 2012-07-11
Enrollment: 193099
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

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:

  1. As of January 1, 1997 they had been diagnosed with diabetes mellitus, were age 40 or older and were members of KPNC,
  2. 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
  3. 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.

Primary outcomes:
measure: Incident Diagnosis of Bladder Cancer (10-year Analysis)
timeFrame: January 1, 1997 to December 31, 2012
Secondary outcomes:
measure: Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis)
timeFrame: January 1, 1997 to December 31, 2012
measure: Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis)
timeFrame: January 1, 1997 to December 31, 2012
measure: Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis)
timeFrame: January 1, 1997 to December 31, 2012
measure: Stage of Bladder Cancer (10 Year Analysis)
timeFrame: January 1, 1997 to December 31, 2012
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.