Fractures, BoneNCT01055223

Fracture Risk With Thiazolidinediones

An observational study of Fractures, Bone and Type II Diabetes, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Fractures, Bone, Type II Diabetes
What is being tested?: TZD only (RSG or PIO or troglitazone), TZD + spironolactone and TZD + amiloride
How many people: 98,483 participants
Where: No sites listed yet
Study dates: May 2009to Mar 2010
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: 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.

Who may be able to join

At least one ICD-9 code for type 2 diabetes
At least 6 months or at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database (The subject's study period begin date will be defined as the earliest date of their first TZD prescription. Subjects included in the study are required to have at least six months of follow-up time in the database prior to their first TZD prescription)

Who cannot join

Subjects with a diagnosis of Paget's disease and osteomalacia
A history of fracture, osteoporosis or cancer prior to the first prescription of TZD (study begin date)

About this study

Official title: The Association Between Exposure to Spironolactone or Amiloride and Fracture Risk Among Subjects Treated With Thiazolidinediones

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.

Read the detailed description

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.

Conditions: Fractures, Bone, Type II Diabetes
Being tested: TZD only (RSG or PIO or troglitazone), TZD + spironolactone, TZD + amiloride
Keywords: thiazolidinediones, rosiglitazone, amiloride, pioglitazone, fracture, Spironolactone
Medical subject headings: Fractures, Bone, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TZD only (RSG or PIO or troglitazone)Drug
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.
TZD + spironolactoneDrug
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.
TZD + amilorideDrug
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.

Study groups in NCT01055223
Study group	Role	What they receive
Type 2 diabetes subjects		Type 2 diabetes subjects Receives: Drug: TZD only (RSG or PIO or troglitazone); Drug: TZD + spironolactone; Drug: TZD + amiloride

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2009Mar 2010

First posted25 Jan 2010 (estimated)
Study startMay 2009
Primary completionMar 2010
Study completionMar 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Fractures, BoneStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Retrospective
Enrolment: 98,483 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01055223
Sponsor's protocol ID: 113332
Status last verified: May 2017
First submitted: 21 Jan 2010
Last updated: 30 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruiting
Biodegradable Magnesium Screws for Unstable Ankle Fracture Surgery
Ankle Fractures, Syndesmotic Injury
Active, not recruitingObservational study
The Developmental Origins of Suicide Mortality
Suicide Mortality
RecruitingObservational study
Duration of Immobilization After Reverse Total Arthroplasty for Proximal Humerus Fractures
Proximal Humeral Fracture, Reverse Total Shoulder Arthroplasty
Recruiting
No Reduction Compared to Closed Reduction for Distal Radius Fractures in Patients Over 65 or Older
Distal Radius Fracture, Casting
RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture

All Fractures, Bone trials

Study at a glance

From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Association Between Exposure to Spironolactone or Amiloride and Fracture Risk Among Subjects Treated With Thiazolidinediones
ClinicalTrials.gov ID: NCT01055223
Acronym / sponsor ID: 113332
Conditions: Fractures, Bone, Type II Diabetes
Keywords: thiazolidinediones, rosiglitazone, amiloride, pioglitazone, fracture, Spironolactone
Study type: Observational
Recruitment status: Completed
Enrolment: 98,483 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: May 2009
Primary completion: Mar 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 25 Jan 2010 (estimated)
Results: Posted 18 Apr 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Case-control
Time perspective: Retrospective
Number of arms: 1

Arm	Type	Receives
Type 2 diabetes subjects	–	Drug: TZD only (RSG or PIO or troglitazone), Drug: TZD + spironolactone, Drug: TZD + amilorideType 2 diabetes subjects

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: 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.

Key inclusion criteria (2 listed)

At least one ICD-9 code for type 2 diabetes
At least 6 months or at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database (The subject's study period begin date will be defined as the earliest date of their first TZD prescription. Subjects included in the study are required to have at least six months of follow-up time in the database prior to their first TZD prescription)

Key exclusion criteria (2 listed)

Subjects with a diagnosis of Paget's disease and osteomalacia
A history of fracture, osteoporosis or cancer prior to the first prescription of TZD (study begin date)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TZD only (RSG or PIO or troglitazone)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.	Drug	Type 2 diabetes subjects
TZD + spironolactoneSubjects 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.	Drug	Type 2 diabetes subjects
TZD + amilorideSubjects 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.	Drug	Type 2 diabetes subjects

Primary outcome

Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD
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
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.
Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD
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
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.

4 secondary outcomes

Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD
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
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
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
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

Results and safety

Results posted to the registry on 18 Apr 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TZD 6-month Cohort (Including TZD 12-month Cohort)	98,483	98,483

Primary outcome: Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD

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. Unit: fractures

Measure	TZD Alone n = 21621	TZD+Spironolactone n = 397	TZD+Amiloride n = 43	Other n = 3
Case	4325	105	12	1
Control	17296	292	31	2

TZD Alone vs TZD+Spironolactone: Odds Ratio (OR): 1.42 (95% CI 1.13 to 1.78)
TZD Alone vs TZD+Spironolactone: Odds Ratio (OR): 1.19 (95% CI 0.93 to 1.52)
TZD Alone vs TZD+Amiloride: Odds Ratio (OR): 1.53 (95% CI 0.78 to 2.98)

Population analysed: Type 2 diabetes patients 18-65 years old exposed to TZD. To be eligible for the study, a subject must have had at least one ICD-9 code for type 2 diabetes and have at least 6 months of exposure to TZD (RSG, PIO, or troglitazone) during their follow-up time available in the database.

Primary outcome: Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD

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. Unit: fractures

Measure	TZD Alone n = 13115	TZD+Spironolactone n = 245	TZD+Amiloride n = 28	Other n = 2
Case	2619	64	8	0
Control	10496	181	20	2

TZD Alone vs TZD+Spironolactone: Odds Ratio (OR): 1.41 (95% CI 1.05 to 1.89)
TZD Alone vs TZD+Spironolactone: Odds Ratio (OR): 1.20 (95% CI 0.88 to 1.65)
TZD Alone vs TZD+Amiloride: Odds Ratio (OR): 1.58 (95% CI 0.69 to 3.60)

Population analysed: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TZD 6-month Cohort	0 of 0	0 of 0	Not reported
TZD-12 Month Cohort	0 of 0	0 of 0	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Fractures, Bone

Not yet recruiting
Biodegradable Magnesium Screws for Unstable Ankle Fracture Surgery
Ankle Fractures, Syndesmotic Injury
Active, not recruitingObservational study
The Developmental Origins of Suicide Mortality
Suicide Mortality
RecruitingObservational study
Duration of Immobilization After Reverse Total Arthroplasty for Proximal Humerus Fractures
Proximal Humeral Fracture, Reverse Total Shoulder Arthroplasty
Recruiting
No Reduction Compared to Closed Reduction for Distal Radius Fractures in Patients Over 65 or Older
Distal Radius Fracture, Casting
RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

An observational study of Fractures, Bone and Type II Diabetes, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01055223.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.