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Trial record 1 of 1 for:    01-03-TL-OPI-524
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Cohort Study of Pioglitazone and Bladder Cancer in Patients With Type II Diabetes

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ClinicalTrials.gov Identifier: NCT01637935
Recruitment Status : Completed
First Posted : July 11, 2012
Results First Posted : October 12, 2012
Last Update Posted : March 7, 2018
Sponsor:
Collaborators:
Kaiser Permanente
Department of Epidemiology at University of Pennsylvania
Information provided by (Responsible Party):
Takeda

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Conditions Diabetes
Bladder Cancer
Intervention Drug: Pioglitazone
Enrollment 193099
Recruitment Details Not applicable (database study)
Pre-assignment Details Not applicable (database study)
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description Patients ever exposed to pioglitazone. Patients never exposed to pioglitazone.
Period Title: Overall Study
Started 34181 158918
Completed 34181 158918
Not Completed 0 0
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group Total
Hide Arm/Group Description Patients ever exposed to pioglitazone. Patients never exposed to pioglitazone. Total of all reporting groups
Overall Number of Baseline Participants 34181 158918 193099
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
40-49 years 29.2 22.1 51.3
50-59 years 33.0 25.6 58.6
60-69 years 25.7 26.2 51.9
70 years and older 12.0 26.1 38.1
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
Female 46.5 46.5 93
Male 53.5 53.5 107
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
White 51.3 52.3 103.6
Black 10.2 10.8 21
Asian 14.8 12.8 27.6
Hispanic 13.4 10.6 24
Other 5.9 5.7 11.6
Missing 4.3 7.8 12.1
Current smoker  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
20.4 17.4 37.8
Renal function at baseline   [1] 
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
Normal creatinine 77.4 77.1 154.5
Elevated creatinine 4.0 8.7 12.7
Missing 18.6 14.1 32.7
[1]
Measure Description: Elevated creatinine: Creatinine >1.4 mg/dL for women and >1.5 mg/dL for men.
Congestive heart failure at baseline  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
3.0 6.9 9.9
Baseline Glycosylated Hemoglobin (HbA1c)  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
<7% 17.1 28.6 45.7
7-7.9% 18.3 19.3 37.6
8-8.9% 12.8 10.4 23.2
9-9.9% 9.7 7.0 16.7
≥10% 23.9 17.1 41
Missing 18.1 17.5 35.6
Newly diagnosed with diabetes mellitus at the start of follow-up   [1] 
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
50.8 57.9 108.7
[1]
Measure Description: Includes newly diagnosed patients and patients who newly enrolled in Kaiser Permanente with an existing diagnosis of diabetes mellitus.
Diabetes duration at baseline  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
0-4 years 60.1 62.8 122.9
5-9 years 9.2 6.0 15.2
10 or more years 9.1 10.9 20
Missing 21.6 20.4 42
Other cancer prior to baseline  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
3.1 5.3 8.4
Other diabetes medications   [1] 
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 34181 participants 158918 participants 193099 participants
Other thiazolidinediones 8.2 1.5 9.7
Metformin 84.8 45.9 130.7
Sulfonylureas 89.8 61.2 151
Other oral hypoglycemic drugs 6.4 1.4 7.8
Insulin 52.7 29.4 82.1
Never treated with any diabetes medication 0.0 14.3 14.3
[1]
Measure Description: Includes use of any other diabetes medications during follow-up.
1.Primary Outcome
Title Incident Diagnosis of Bladder Cancer (10-year Analysis)
Hide Description Incident bladder cancers were identified from January 1, 1997 to December 31, 2012.
Time Frame January 1, 1997 to December 31, 2012
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants.
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description:
Patients ever exposed to pioglitazone.
Patients never exposed to pioglitazone.
Overall Number of Participants Analyzed 34181 158918
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100,000 person years
89.8
(76.9 to 102.7)
75.9
(71.3 to 80.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Fully adjusted refers to inclusion of all potential confounders in the statistical model from the 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder cancer, renal insufficiency, HbA1c and the interaction with new diagnosis of diabetes, duration of diabetes, and year of cohort entry.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.10
Confidence Interval 95%
0.92 to 1.31
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Fully adjusted adding the proteinuria testing variable.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.06
Confidence Interval 95%
0.89 to 1.26
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis)
Hide Description [Not Specified]
Time Frame January 1, 1997 to December 31, 2012
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description:
Patients ever exposed to pioglitazone.
Patients never exposed to pioglitazone.
Overall Number of Participants Analyzed 34181 158918
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100,000 person years
Less than 4.5 years
68.2
(54.0 to 82.5)
NA [1] 
(NA to NA)
4.5 -8.5 years
111.6
(84.5 to 138.7)
NA [1] 
(NA to NA)
More than 8.0 years
125.8
(82.9 to 168.7)
NA [1] 
(NA to NA)
[1]
Not calculated for the No Pioglitazone Treatment group.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Time since starting pioglitazone <4.5 years vs unexposed group. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval 95%
0.71 to 1.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Time since starting pioglitazone 4.5-8 years vs unexposed group. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval 95%
0.93 to 1.59
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Time since starting pioglitazone >8 years vs unexposed group. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.20
Confidence Interval 95%
0.83 to 1.75
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis)
Hide Description [Not Specified]
Time Frame January 1, 1997 to December 31, 2012
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants.
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description:
Patients ever exposed to pioglitazone.
Patients never exposed to pioglitazone.
Overall Number of Participants Analyzed 34181 158918
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100,000 person years
Less than 1.5 years
67.5
(50.4 to 84.6)
NA [1] 
(NA to NA)
1.5 - 4.0 years
88.4
(67.5 to 109.3)
NA [1] 
(NA to NA)
More than 4 years
113.7
(84.2 to 143.2)
NA [1] 
(NA to NA)
[1]
Not calculated for the No Pioglitazone Treatment group.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Duration of therapy <1.5 years. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval 95%
0.68 to 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Duration of therapy 1.5-4 years. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval 95%
0.80 to 1.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Duration of therapy >4 years. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval 95%
0.87 to 1.54
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis)
Hide Description [Not Specified]
Time Frame January 1, 1997 to December 31, 2012
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants.
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description:
Patients ever exposed to pioglitazone.
Patients never exposed to pioglitazone.
Overall Number of Participants Analyzed 34181 158918
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: events per 100,000 person years
1 - 14000 mg
69.1
(52.4 to 85.8)
NA [1] 
(NA to NA)
14001 - 40000 mg
96.9
(74.0 to 119.8)
NA [1] 
(NA to NA)
>40000 mg
101.4
(73.5 to 129.2)
NA [1] 
(NA to NA)
[1]
Not calculated for the No Pioglitazone Treatment group.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Cumulative dose 1–14000 mg. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval 95%
0.69 to 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Cumulative dose 14001–40000 mg. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval 95%
0.85 to 1.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone Exposed Group, Pioglitazone Unexposed Group
Comments Cumulative dose >40000 mg. Fully adjusted including all potential confounders in statistical model from 5-year interim report plus year of cohort entry: age, sex, race/ethnicity, other diabetes medications, smoking, other bladder conditions, median household income, congestive heart failure, cancer other than bladder, renal insufficiency, HbA1c and interaction with new diagnosis of diabetes, duration of diabetes, year of cohort entry and proteinuria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.07
Confidence Interval 95%
0.79 to 1.44
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Stage of Bladder Cancer (10 Year Analysis)
Hide Description [Not Specified]
Time Frame January 1, 1997 to December 31, 2012
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants diagnosed with bladder cancer.
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description:
Patients ever exposed to pioglitazone.
Patients never exposed to pioglitazone.
Overall Number of Participants Analyzed 186 1075
Measure Type: Number
Unit of Measure: percentage of participants
PUNLMP 1 1
In situ 50 49
Local 40 38
Regional 4 6
Distant 2 3
Undetermined 3 3
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events not applicable as this study is based on the secondary use of electronic medical records.
 
Arm/Group Title Pioglitazone Exposed Group Pioglitazone Unexposed Group
Hide Arm/Group Description Patients ever exposed to pioglitazone. Patients never exposed to pioglitazone.
All-Cause Mortality
Pioglitazone Exposed Group Pioglitazone Unexposed Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pioglitazone Exposed Group Pioglitazone Unexposed Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pioglitazone Exposed Group Pioglitazone Unexposed Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
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 first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 45 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Head, Pharmacoepidemiology
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01637935     History of Changes
Other Study ID Numbers: 01-03-TL-OPI-524
U1111-1132-3482 ( Registry Identifier: WHO )
First Submitted: July 7, 2012
First Posted: July 11, 2012
Results First Submitted: August 31, 2012
Results First Posted: October 12, 2012
Last Update Posted: March 7, 2018