Thiazolidinedione Intervention With Vitamin D Evaluation

Diabetes Mellitus, Type 2 Clinical Trial

— TIDE  

Official title:

AVANDIA CV Outcomes Study: Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) A Multicenter Randomized Double-Blind Placebo-Controlled Trial of a Thiazolidinedione or Placebo and of Vitamin D or Placebo In People With Type 2 Diabetes at Risk For Cardiovascular Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00879970
• Other study ID #: 111960
• Status: Terminated
• Phase: Phase 4
• First received: April 2, 2009
• Last updated: October 3, 2016
• Start date: May 2009
• Est. completion date: November 2010

Study information

• Verified date: September 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will answer two separate questions.

The first question is to test the cardiovascular effects of long-term treatment with rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease.

The second question will compare the effects of long-term supplementation of vitamin D on death and cancer

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1332
• Est. completion date: November 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) greater than or equal to 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes

• Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening

• Age = 50 years and evidence of vascular disease defined as =1of:

• prior myocardial infarction

• prior stroke

• coronary, carotid or peripheral artery revascularization = 4 years earlier

• previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation OR

• Age = 55 years and evidence of subclinical vascular disease defined as =1 of:

• microalbuminuria or proteinuria

• history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ECG) or echocardiogram

• 50% stenosis on any imaging of coronary, carotid or lower extremity arteries

• ankle/brachial index <0.9 OR

• Age = 60 years and at least 2 of the following cardiovascular disease risk factors:

• current tobacco use

• LDL-c =3.4 mmol/L (130 mg/dL) or on a lipid lowering medication

• HDL-c < 1.0 mmol/L (40 mg/dL) for men and < 1.3 mmol/L (50 mg/dL) for women or triglycerides = 2.3 mmol/L (200 mg/dL)

• BP lowering medication use or untreated SBP = 140 mmHg or DBP = 95 mmHg

• Waist to hip ratio > 1.0 for men and > 0.8 for women

• On no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the MOP) with stable dosing for 10 weeks prior to screening

Exclusion Criteria:

• Type 1 diabetes

• Current need for insulin treatment

• Symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician

• An acute cardiovascular event within 30 days prior to randomization

• Symptomatic heart failure (i.e. New York Heart Association class II or higher) or any episode of previous pulmonary edema or known ejection fraction < 0.4 or current use of loop diuretics

• Any fracture within the past 1 year

• Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery

• Coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, MI, or stroke in the intervening period

• End stage renal disease requiring renal replacement therapy

• Receiving drug therapy to treat liver disease

• A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer (other than prophylactic)

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 2.5 times the upper limit of normal

• A prior heart transplant or awaiting a heart transplant

• Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin D therapy

• Regular use of or indication for greater than 400IU of vitamin D daily

• Clinically or medically unstable with expected survival < 1 year

• Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data

• Any other factor likely to limit protocol compliance or reporting of adverse events

• Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator

• Contraindications to or history of hypersensitivity to the investigational products

• History of renal stones within the past 2 years

• Participation in another clinical trial of an investigational agent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• pioglitazone
Pioglitazone30 mg and 45 mg tablets are over-encapsulated with Swedish orange size DB-AA capsule shell.
• rosiglitazone
Rosiglitazone 4 mg and 8 mg tablets are over-encapsulated with Swedish orange size DB-AA capsule shell.
• placebo
Placebo to match is Swedish orange size DB-AA capsule filled with white to off-white non-active powder blend.

Dietary Supplement:
• Vitamin D
Vitamin D factor intervention
• Placebo
Vitamin D factor intervention

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Coronel Suarez	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Salta
Argentina	GSK Investigational Site	San Miguel de Tucuman
Argentina	GSK Investigational Site	San Nicolas	Buenos Aires
Argentina	GSK Investigational Site	Zárate
Canada	GSK Investigational Site	Barrie	Ontario
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Cambridge	Ontario
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Hamilton.	Ontario
Canada	GSK Investigational Site	Laval	Quebec
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Ohsweken	Ontario
Canada	GSK Investigational Site	Oshawa	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Rimouski	Quebec
Canada	GSK Investigational Site	Saint John's	Newfoundland and Labrador
Canada	GSK Investigational Site	Saint-Georges	Quebec
Canada	GSK Investigational Site	Sainte-Foy	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Surrey	British Columbia
Canada	GSK Investigational Site	Thornhill	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Winnipeg	Manitoba
Canada	GSK Investigational Site	Winnipeg	Manitoba
Canada	GSK Investigational Site	Winnipeg	Manitoba
Chile	GSK Investigational Site	Osorno
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Chile	GSK Investigational Site	Valdivia
Chile	GSK Investigational Site	Victoria
Colombia	GSK Investigational Site	Armenia
Colombia	GSK Investigational Site	Barrangquilla
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Bogotac
Colombia	GSK Investigational Site	Cali
Colombia	GSK Investigational Site	Cartagena
Colombia	GSK Investigational Site	Cartagena
Colombia	GSK Investigational Site	Espinal
Colombia	GSK Investigational Site	Floridablanca
Colombia	GSK Investigational Site	Manizales
Colombia	GSK Investigational Site	Medellín
Colombia	GSK Investigational Site	Pereira
Czech Republic	GSK Investigational Site	Havirov
Czech Republic	GSK Investigational Site	Jihlava
Czech Republic	GSK Investigational Site	Mestec Kralove
Czech Republic	GSK Investigational Site	Ostrava
Czech Republic	GSK Investigational Site	Prague
Czech Republic	GSK Investigational Site	Praha
Czech Republic	GSK Investigational Site	Praha 4
Czech Republic	GSK Investigational Site	Praha 5
Czech Republic	GSK Investigational Site	Praha 5
Czech Republic	GSK Investigational Site	Praha 6
Czech Republic	GSK Investigational Site	Pribram 8
Czech Republic	GSK Investigational Site	Rakovnik
Czech Republic	GSK Investigational Site	Uherske Hradiste
Denmark	GSK Investigational Site	Aarhus-N
Denmark	GSK Investigational Site	Frederiksberg
Denmark	GSK Investigational Site	Glostrup
Denmark	GSK Investigational Site	Hellerup
Denmark	GSK Investigational Site	Herlev
Denmark	GSK Investigational Site	København NV
Denmark	GSK Investigational Site	Koebenhavn
Denmark	GSK Investigational Site	Odense C
Denmark	GSK Investigational Site	Viborg
Finland	GSK Investigational Site	Helsinski
Finland	GSK Investigational Site	Kuopio
Finland	GSK Investigational Site	Oulu
Germany	GSK Investigational Site	Angermuende	Brandenburg
Germany	GSK Investigational Site	Augsburg	Bayern
Germany	GSK Investigational Site	Bad Oeynhausen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bergkamen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Borna	Sachsen
Germany	GSK Investigational Site	Deggingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Delitzsch	Sachsen
Germany	GSK Investigational Site	Dorsten	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Elsterwerda	Brandenburg
Germany	GSK Investigational Site	Eschweiler	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Gars am Inn	Bayern
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Grossalmerode	Hessen
Germany	GSK Investigational Site	Haag	Bayern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Ingelheim	Rheinland-Pfalz
Germany	GSK Investigational Site	Kelkheim	Hessen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koethen	Sachsen-Anhalt
Germany	GSK Investigational Site	Kuenzing	Bayern
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Neunkirchen	Saarland
Germany	GSK Investigational Site	Oschatz	Sachsen
Germany	GSK Investigational Site	Pirna	Sachsen
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Schoenebeck	Sachsen-Anhalt
Germany	GSK Investigational Site	Villingen-Schwenningen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Vilshofen	Bayern
Germany	GSK Investigational Site	Wallerfing	Bayern
Germany	GSK Investigational Site	Wangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Winsen/Lohe	Niedersachsen
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wolmirstedt	Sachsen-Anhalt
Germany	GSK Investigational Site	Zerbst	Sachsen-Anhalt
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Banjara Hills PO, Hyderabad
India	GSK Investigational Site	Belgaum
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Cochin
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Karnal
India	GSK Investigational Site	Kerala
India	GSK Investigational Site	Kochi
India	GSK Investigational Site	Kochi
India	GSK Investigational Site	Kottyam
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	Nasik
India	GSK Investigational Site	Nellore
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Tamil Nadu
India	GSK Investigational Site	Trivandrum
India	GSK Investigational Site	Vijayawada
Italy	GSK Investigational Site	Chieri (Torino)
Italy	GSK Investigational Site	Milano (Milan)	Lombardia
Italy	GSK Investigational Site	Pozzilli (IS)	Molise
Italy	GSK Investigational Site	Sesto San Giovanni (MI)	Lombardia
Latvia	GSK Investigational Site	Cesis
Latvia	GSK Investigational Site	Daugavpils
Latvia	GSK Investigational Site	Jekabpils
Latvia	GSK Investigational Site	Liepaja
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Tukums
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Guadalajara
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Morelia	Michoacán
Mexico	GSK Investigational Site	San Luis Potosi	San Luis Potosí
Mexico	GSK Investigational Site	Tampico
Mexico	GSK Investigational Site	Tijuana	Baja California Norte
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Hoofddorp
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Norway	GSK Investigational Site	Bodø
Norway	GSK Investigational Site	Hoenefoss
Norway	GSK Investigational Site	Kløfta
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Skedsmokorset
Norway	GSK Investigational Site	Stavanger
Norway	GSK Investigational Site	Tromsø
Norway	GSK Investigational Site	Trondheim
Pakistan	GSK Investigational Site	Faisalabad
Pakistan	GSK Investigational Site	Islamabad
Pakistan	GSK Investigational Site	Lahore
Peru	GSK Investigational Site	Arequipa
Philippines	GSK Investigational Site	Laoag City
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Baia Mare
Romania	GSK Investigational Site	Bistrita
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Buzau
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Oradea
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Sibiu
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kirov
Russian Federation	GSK Investigational Site	Kursk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Nizhny Novgorod
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St Pertersburg
Russian Federation	GSK Investigational Site	St Petersberg
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Syktyvkar
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Vladivostok
Russian Federation	GSK Investigational Site	Vladivostok
Russian Federation	GSK Investigational Site	Volgograd
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Nitra
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Benoni
South Africa	GSK Investigational Site	Bloemfontein
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Chatsworth	KwaZulu- Natal
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Meyerspark	Gauteng
South Africa	GSK Investigational Site	Newton
South Africa	GSK Investigational Site	Observatory
South Africa	GSK Investigational Site	Parktown
South Africa	GSK Investigational Site	Parktown	Gauteng
South Africa	GSK Investigational Site	Port Elizabeth	Eastern Cape
South Africa	GSK Investigational Site	Pretoria
South Africa	GSK Investigational Site	Somerset West
South Africa	GSK Investigational Site	Soweto
South Africa	GSK Investigational Site	Soweto
South Africa	GSK Investigational Site	Umhlanga Rocks	KwaZulu- Natal
South Africa	GSK Investigational Site	Worcester
Sweden	GSK Investigational Site	Eksjö
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Härnösand
Sweden	GSK Investigational Site	Karlshamn
Sweden	GSK Investigational Site	Kristianstad
Sweden	GSK Investigational Site	Ljungby
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Oskarshamn
Sweden	GSK Investigational Site	Skene
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Vällingby
Sweden	GSK Investigational Site	Växjö
Thailand	GSK Investigational Site	Bangkok
United Kingdom	GSK Investigational Site	Bath	Somerset
United Kingdom	GSK Investigational Site	Chippenham
United Kingdom	GSK Investigational Site	Doncaster
United Kingdom	GSK Investigational Site	Harrogate
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Sheffield
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Haverhill	Massachusetts
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Kalispell	Montana
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Northridge	California
United States	GSK Investigational Site	Pocatella	Idaho
United States	GSK Investigational Site	Pocatello	Idaho
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Tucker	Georgia
United States	GSK Investigational Site	Westfield	New York

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Academic Research Collaborator: Population Health Research Institute / Hamilton Health

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Colombia,  Czech Republic,  Denmark,  Finland,  Germany,  India,  Italy,  Latvia,  Mexico,  Netherlands,  Norway,  Pakistan,  Peru,  Philippines,  Romania,  Russian Federation,  Slovakia,  South Africa,  Sweden,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)	An event adjudication committee (EAC) adjudicated all occurrences of the components of the composite cardiovascular (CV; related to heart) outcome for TZD. Components are the first occurrence of cardiovascular death for which a non-heart-related cause has not been identified; non-fatal myocardial infarction (MI) (death of heart muscle from sudden blockage of a coronary artery by blood clot not leading to death); and non-fatal stroke (rapidly developing loss of brain function[s] due to disturbance in the blood supply to the brain not leading to death).	From Randomization at Visit 3 up to the Final Visit (average of 162 days)	Yes
Primary	Number of Participants With the Indicated Components of the Composite Outcome for Vitamin D	An EAC adjudicated all occurrences of the components of the composite outcome for vitamin D. Components are the first occurrence of death or cancer requiring hospitalization, treatment with medicines (chemotherapy), or surgery.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Any Revascularization	Revascularization is defined as any surgical procedure for the provision of a new, additional, or augmented blood supply to heart muscle. Data regarding the need for any revascularization were adjudicated by the EAC and sent to the data monitoring committee (IDMC) on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Need for Hospitalization for Any Reason	Data regarding the need for hospitalization for any reason were collected and were then forwarded to the independent data monitoring committee (IDMC) on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Need for Hospitalization for Congestive Heart Failure (CHF), Shortness of Breath, Pneumonia, or Angina	CHF is a condition in which the heart is not able to pump adequate blood to meet the body's needs. Shortness of breath is defined as difficulty in breathing. Pneumonia is an infection of the lungs, caused by various microorganisms. Angina is defined as severe chest pain due to lack of adequate blood supply of the heart muscle because of obstruction/spasm of the heart's blood vessels. Data regarding the need for hospitalization due to any of these reasons were adjudicated by the EAC and sent to the IDMC on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Composite Microvascular Outcome	The components of the composite microvascular outcome are retinopathy, decline in eGFR, vitrectomy, and renal replacement surgery. Retinopathy is defined as damage to the inner lining of the eye (retina). Decline in eGFR is defined as a >=30% reduction in kidney function. Vitrectomy is a surgery to remove some or all of the fluid (vitreous humor) from the eye. Renal replacement therapy includes all the life-supporting treatments for renal failure. Data regarding the number of participants with changes in micro blood vessels (composite microvascular outcome) were collected at each visit.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Retinopathy Requiring Laser Therapy, a Decline in Estimated Glomerular Filtration Rate (eGFR), Vitrectomy, and Renal Replacement Therapy	Retinopathy is defined as damage to the inner lining of the eye (retina). Decline in eGFR is defined as a >=30% reduction in kidney function. Vitrectomy is a surgery to remove some or all of the fluid (vitreous humor) from the eye. Renal replacement therapy includes all the life-supporting treatments for renal failure. Data on the number of participants with all of these microvascular outcomes were collected at each visit. Data regarding the number of participants with these microvascular outcomes were adjudicated by the EAC and sent to the IDMC on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Severe Lower Than Normal Blood Glucose Level (Hypoglycemia)	Severe hypoglycemia is defined as hypoglycemia requiring assistance from another person with either a documented plasma glucose <=36 mg/deciliter (2.0 millimole per liter [mmol/L]) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration. Hypoglycemia data were obtained from outcomes reported by the site. Data regarding hypoglycemia were adjudicated by the EAC and sent to the IDMC on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Clinical Proteinuria	Clinical proteinuria is defined as a laboratory detection of urinary protein excretion > 0.5 grams (g) per 24 hours; spot urine analysis for albumin:creatinine ratio >=300 milligrams/g; timed urine collection for albumin excretion >=200 µg/minute or >=300 mg/24 hours. Clinical proteinuria data were obtained from outcomes reported by the site.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With a Fracture	Fracture is defined as a medical condition in which there is a break in the continuity of the bone. Fractures are defined as those breaks that are self reported plus confirmed by an X-ray. Data regarding all occurrences of any fracture were adjudicated by the EAC and sent to the IDMC on a regular basis for unblinded review.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Hepatic Enzyme Increased or Abnormal Liver Function Tests	Liver function tests are groups of clinical biochemistry laboratory blood assays designed to give information about the health of the liver. "Liver function test abnormal" and "hepatic enzyme increased" were obtained from adverse event data as reported by investigators based on the reference range of the reporting local laboratory methodology. The vitamin D arm was not analyzed for this outcome measure.	From Randomization at Visit 3 to Final Visit (up to 162 days)	Yes
Secondary	Number of Participants With Cognitive (Mental Processes) Decline (CD) From Baseline to the Year 2 Visit and the Final Visit	CD is equivalent to a difference of >=1.5 units on the Digit Symbol Substitution Test (DSST) score. The DSST is a neuropsychological test sensitive to brain damage, a serious loss of cognitive ability, age, and depression. It consists of digit-symbol pairs, followed by a list of digits. Under each digit the participant was asked to write the corresponding symbol as quickly as possible. The number of correct symbols within the allowed time (90 or 120 seconds) was measured in units (one correct score equals one unit).	From Randomization at Visit 3 to Final Visit (up to 162 days)	No
Secondary	Number of Participants With Erectile Dysfunction	Erectile dysfunction (ED) is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance. ED was assessed by using the International Index of Erectile Dysfunction (IIED) questionnaire. This standardized and validated 15-item self-evaluation scale provides pre- and post-treatment clinic evaluations of erectile and orgasmic function, sexual desire, satisfaction with sexual intercourse, and general satisfaction.	From Randomization at Visit 3 to Final Visit (up to 162 days)	No
Secondary	Mean Score on Euro-QoL (EQ)-5D	Quality of life (QoL) was assessed by using the Euro-QoL (EQ)-5D, a short questionnaire used for measuring health-related QoL. The preference weights are elicited by asking participants to place hypothetical health states on a visual analogue scale from "0" to "1", whereby a score of "1" represents the best health state imaginable and "0" represents a health state equivalent to being dead. Negative states are those worse than being dead.	From Randomization at Visit 3 to Final Visit (up to 162 days)	No
Secondary	Mean Score on Montreal Cognitive Assessment (MoCA) Test, as an Assessment of Cognitive Function (CF)	CF was assessed with the 30-point (pt) MoCA test, involving a short-term memory recall task (T) (5 pts), a clock-drawing T (3 pts), a 3-dimensional cube copy (1 pt), a trail-making B T (1 pt), a phonemic fluency T (1 pt), a 2-item verbal abstraction T (2 pts), an attention T (1 pt), a serial subtraction T (3 pts), digits forward/ backward (1 pt each), a 3-item confrontation naming T (3 pts), repetition of 2 syntactically complex sentences (2 pts), and orientation to time/ place (6 pts). A score of 26 or above is normal.	From Randomization at Visit 3 to Final Visit (up to 162 days)	No

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.