An observational study in Fractures, Bone and Type II Diabetes, sponsored by GlaxoSmithKline. Completed. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-05-30.
Sponsored by GlaxoSmithKline · Observational
Treatment with thiazolidinediones (TZD) has recently been reported to possibly increase the risk of fractures in a randomized trial exploring the efficacy of rosiglitazone (RSG), metformin, or glyburide encompassing 4360 patients with type 2 diabetes.
It is hypothesized that spironolactone, a diuretic that is broadly used for the treatment of fluid retention and edema associated with TZD, has a potential protective effect against bone fractures. However, to our knowledge, this has not been tested in diabetic patients treated with TZD. Amiloride is another diuretic that shares with spironolactone the anti mineralocorticoid ion gated channels activity and will be analysed in this study with regard to possible protective effect against bone fracture in combination with TZD.
This study is a nested case-control study conducted among type 2 diabetes subjects exposed to TZD. The study aims to explore if the risk of fracture is reduced among type 2 diabetic subjects exposed to spironolactone and TZD. The study will compare the odds of any low impact fracture, and hand, foot, upper arm, wrist, and hip fracture incidence in subjects treated with TZD+spironolactone and TZD+amiloride compared to subjects treated with TZD only.
The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed to TZD. To be eligible for the study, a subject must have had at least one International Classification of Disease (ICD)-9 code for type 2 diabetes and have at least 6 months or at least 12 months of exposure to TZD (rosiglitazone [RSG], pioglitazone [PIO] or troglitazone) during their follow-up time available in the database.
Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.
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The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed to TZD for at least 6 months or at least 12 months. The study will use data from the US health claims database, the Ingenix Impact National Managed Care Database (Impact Database). The Impact Database system is a comprehensive, de-identified U.S. healthcare claims database that is representative of the non-elderly, insurance-carrying population. It includes 89.3 million lives from 1997 to 2008. Approximately 74 percent of all patients in the database have pharmacy benefits and, on average, 25 months of enrollment/claims information. The data are collected from over 46 different healthcare plans serving members across nine census regions.
Exclusion Criteria:
Type 2 diabetes subjects
Drug: TZD only (RSG or PIO or troglitazone) · Drug: TZD + spironolactone · Drug: TZD + amiloride
Drug exposure will be inferred from prescription claims. Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.
Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and spirinolactone must overlap by at least 30 days.
Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and Amiloride must overlap by at least 30 days.
Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD
ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 and December 31, 2008
Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD
ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD
ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 12 Months of Exposure to TZD
ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
Number of Hip Fractures Combined in Males and Females After 6 Months of Exposure to TZD
ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
Number of Hip Fractures Combined in Males and Females After 12 Months of Exposure to TZD
ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
Time frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
| Milestone | TZD 6-month Cohort (Including TZD 12-month Cohort) |
|---|---|
| Started | 98483 |
| Completed | 98483 |
| Not completed | 0 |
ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 4325 | 105 | 12 | 1 |
| Control | 17296 | 292 | 31 | 2 |
ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 2619 | 64 | 8 | 0 |
| Control | 10496 | 181 | 20 | 2 |
ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 2163 | 48 | 2 | 1 |
| Control | 8615 | 148 | 18 | 2 |
ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 1285 | 29 | 0 | 0 |
| Control | 5115 | 94 | 12 | 2 |
ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 92 | 6 | — | — |
| Control | 387 | 4 | — | — |
ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
| fractures | TZD Alone | TZD+Spironolactone | TZD+Amiloride | Other |
|---|---|---|---|---|
| Case | 44 | 2 | — | — |
| Control | 182 | 1 | — | — |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TZD 6-month Cohort | — | — | — |
| TZD-12 Month Cohort | — | — | — |
| Age, Continuous(Years) | TZD 6-month Cohort (Including TZD 12-month Cohort) |
|---|---|
| Mean | 52.2 ± 8.33 |
| Sex: Female, Male(Participants) | TZD 6-month Cohort (Including TZD 12-month Cohort) |
|---|---|
| Female | 37738 |
| Male | 60745 |
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