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TIDE: Thiazolidinedione Intervention With Vitamin D Evaluation

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Terminated
CT.gov ID
NCT00879970
Collaborator
Population Health Research Institute (Other)
1,332
Enrollment
331
Locations
5
Arms
18
Duration (Months)
4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
1332 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Study Start Date :
May 1, 2009
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Nov 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: pioglitazone

PIO tablet was administered in the dose of 30 milligrams (mg) OD initially and could be titrated to a maximum dose of 45 mg at or after the 6-month visit. After 1 year of treatment, the dose of PIO was increased to 45 mg OD for the duration of 5.5 years.

Drug: pioglitazone
Pioglitazone30 mg and 45 mg tablets are over-encapsulated with Swedish orange size DB-AA capsule shell.
Active Comparator: rosiglitazone

RSG tablet was administered in the dose of 4 mg OD initially and could be titrated to a maximum dose of 8 mg at or after the 6-month visit. After 1 year of treatment, the dose of RSG was increased to 8 mg OD for the duration of 5.5 years.

Drug: rosiglitazone
Rosiglitazone 4 mg and 8 mg tablets are over-encapsulated with Swedish orange size DB-AA capsule shell.
Placebo Comparator: TZD placebo

Matching placebo tablet was administered once a day (OD) for the duration of 5.5 years

Drug: placebo
Placebo to match is Swedish orange size DB-AA capsule filled with white to off-white non-active powder blend.
Active Comparator: Vitamin D

Active comparator

Dietary Supplement: Vitamin D
Vitamin D factor intervention
Placebo Comparator: Vitamin D placebo

Placebo Comparator

Dietary Supplement: Placebo
Vitamin D factor intervention

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD) [From Randomization at Visit 3 up to the Final Visit (average of 162 days)]

    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).

  2. Number of Participants With the Indicated Components of the Composite Outcome for Vitamin D [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

Secondary Outcome Measures

  1. Number of Participants With Any Revascularization [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  2. Number of Participants With Need for Hospitalization for Any Reason [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  3. Number of Participants With Need for Hospitalization for Congestive Heart Failure (CHF), Shortness of Breath, Pneumonia, or Angina [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  4. Number of Participants With Composite Microvascular Outcome [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  5. Number of Participants With Retinopathy Requiring Laser Therapy, a Decline in Estimated Glomerular Filtration Rate (eGFR), Vitrectomy, and Renal Replacement Therapy [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  6. Number of Participants With Severe Lower Than Normal Blood Glucose Level (Hypoglycemia) [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  7. Number of Participants With Clinical Proteinuria [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  8. Number of Participants With a Fracture [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  9. Number of Participants With Hepatic Enzyme Increased or Abnormal Liver Function Tests [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  10. Number of Participants With Cognitive (Mental Processes) Decline (CD) From Baseline to the Year 2 Visit and the Final Visit [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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).

  11. Number of Participants With Erectile Dysfunction [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  12. Mean Score on Euro-QoL (EQ)-5D [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

  13. Mean Score on Montreal Cognitive Assessment (MoCA) Test, as an Assessment of Cognitive Function (CF) [From Randomization at Visit 3 to Final Visit (up to 162 days)]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
  1. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Long Beach California United States 90822
2 GSK Investigational Site Los Angeles California United States 90033
3 GSK Investigational Site Northridge California United States 91324
4 GSK Investigational Site San Diego California United States 92109
5 GSK Investigational Site Decatur Georgia United States 30033
6 GSK Investigational Site Tucker Georgia United States 30084
7 GSK Investigational Site Pocatella Idaho United States 83209
8 GSK Investigational Site Pocatello Idaho United States 83201
9 GSK Investigational Site New Orleans Louisiana United States 70112
10 GSK Investigational Site Haverhill Massachusetts United States 1830
11 GSK Investigational Site Minneapolis Minnesota United States 55454
12 GSK Investigational Site St. Louis Missouri United States 63106
13 GSK Investigational Site Kalispell Montana United States 59901
14 GSK Investigational Site Westfield New York United States 14787
15 GSK Investigational Site Durham North Carolina United States 27710
16 GSK Investigational Site Cleveland Ohio United States 44195
17 GSK Investigational Site Portland Oregon United States 97216
18 GSK Investigational Site Portland Oregon United States 97239
19 GSK Investigational Site Kingsport Tennessee United States 37660
20 GSK Investigational Site Memphis Tennessee United States 38104
21 GSK Investigational Site Dallas Texas United States 75246
22 GSK Investigational Site Houston Texas United States 77030
23 GSK Investigational Site Temple Texas United States 76508
24 GSK Investigational Site Ciudad Autonoma de Buenos Aires Buenos Aires Argentina 1090
25 GSK Investigational Site Coronel Suarez Buenos Aires Argentina
26 GSK Investigational Site Mar del Plata Buenos Aires Argentina 7600
27 GSK Investigational Site San Nicolas Buenos Aires Argentina B2900DMH
28 GSK Investigational Site Buenos Aires Argentina 1405
29 GSK Investigational Site Salta Argentina 4400
30 GSK Investigational Site San Miguel de Tucuman Argentina 4000
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32 GSK Investigational Site Calgary Alberta Canada T2T 5C7
33 GSK Investigational Site Calgary Alberta Canada T3S OM3
34 GSK Investigational Site Edmonton Alberta Canada T5A 4L8
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40 GSK Investigational Site Saint John's Newfoundland and Labrador Canada A1B 3V6
41 GSK Investigational Site Halifax Nova Scotia Canada B3H 2Y9
42 GSK Investigational Site Barrie Ontario Canada L4M 7G1
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48 GSK Investigational Site London Ontario Canada N6A 4V2
49 GSK Investigational Site Mississauga Ontario Canada L5M 2V8
50 GSK Investigational Site Ohsweken Ontario Canada N0A 1M0
51 GSK Investigational Site Oshawa Ontario Canada L1J 2K1
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53 GSK Investigational Site Ottawa Ontario Canada K1H 1A2
54 GSK Investigational Site Thornhill Ontario Canada L4J 8L7
55 GSK Investigational Site Toronto Ontario Canada M4R 2G4
56 GSK Investigational Site Toronto Ontario Canada M5C 2T2
57 GSK Investigational Site Toronto Ontario Canada M9L 1W9
58 GSK Investigational Site Laval Quebec Canada H7T 2P5
59 GSK Investigational Site Montreal Quebec Canada H2W 1R7
60 GSK Investigational Site Quebec City Quebec Canada G1J 1Z6
61 GSK Investigational Site Quebec City Quebec Canada G1L 3L5
62 GSK Investigational Site Quebec City Quebec Canada G1V 4G5
63 GSK Investigational Site Rimouski Quebec Canada G5L 5T1
64 GSK Investigational Site Saint-Georges Quebec Canada G5Y 4T8
65 GSK Investigational Site Sainte-Foy Quebec Canada G1V 4G2
66 GSK Investigational Site Sherbrooke Quebec Canada J1H 5N4
67 GSK Investigational Site Temuco Región De La Araucania Chile
68 GSK Investigational Site Santiago Región Metro De Santiago Chile 8330024
69 GSK Investigational Site Santiago Región Metro De Santiago Chile 8331143
70 GSK Investigational Site Santiago Región Metro De Santiago Chile
71 GSK Investigational Site Osorno Chile
72 GSK Investigational Site Valdivia Chile
73 GSK Investigational Site Victoria Chile
74 GSK Investigational Site Armenia Colombia
75 GSK Investigational Site Barrangquilla Colombia
76 GSK Investigational Site Barranquilla Colombia
77 GSK Investigational Site Bogotac Colombia 83012
78 GSK Investigational Site Bogota Colombia
79 GSK Investigational Site Cali Colombia
80 GSK Investigational Site Cartagena Colombia 71 31-315
81 GSK Investigational Site Cartagena Colombia
82 GSK Investigational Site Espinal Colombia
83 GSK Investigational Site Floridablanca Colombia
84 GSK Investigational Site Manizales Colombia
85 GSK Investigational Site Medellín Colombia
86 GSK Investigational Site Pereira Colombia
87 GSK Investigational Site Havirov Czech Republic 736 01
88 GSK Investigational Site Jihlava Czech Republic 586 01
89 GSK Investigational Site Mestec Kralove Czech Republic 289 03
90 GSK Investigational Site Ostrava Czech Republic 70030
91 GSK Investigational Site Prague Czech Republic 181 00
92 GSK Investigational Site Praha 4 Czech Republic 140 21
93 GSK Investigational Site Praha 5 Czech Republic 150 00
94 GSK Investigational Site Praha 5 Czech Republic 158 00
95 GSK Investigational Site Praha 6 Czech Republic 160 00
96 GSK Investigational Site Praha Czech Republic 102 00
97 GSK Investigational Site Pribram 8 Czech Republic 261 01
98 GSK Investigational Site Rakovnik Czech Republic 269 01
99 GSK Investigational Site Uherske Hradiste Czech Republic 68601
100 GSK Investigational Site Aarhus-N Denmark 8200
101 GSK Investigational Site Frederiksberg Denmark 2000
102 GSK Investigational Site Glostrup Denmark 2600
103 GSK Investigational Site Hellerup Denmark 2900
104 GSK Investigational Site Herlev Denmark DK-2730
105 GSK Investigational Site Koebenhavn Denmark 2300
106 GSK Investigational Site København NV Denmark 2400
107 GSK Investigational Site Odense C Denmark 5000
108 GSK Investigational Site Viborg Denmark 8800
109 GSK Investigational Site Helsinski Finland 00260
110 GSK Investigational Site Kuopio Finland 70210
111 GSK Investigational Site Oulu Finland 90100
112 GSK Investigational Site Deggingen Baden-Wuerttemberg Germany 73326
113 GSK Investigational Site Villingen-Schwenningen Baden-Wuerttemberg Germany 78048
114 GSK Investigational Site Wangen Baden-Wuerttemberg Germany 88239
115 GSK Investigational Site Weinheim Baden-Wuerttemberg Germany 69469
116 GSK Investigational Site Augsburg Bayern Germany 86150
117 GSK Investigational Site Gars am Inn Bayern Germany 83536
118 GSK Investigational Site Haag Bayern Germany 83527
119 GSK Investigational Site Kuenzing Bayern Germany 94550
120 GSK Investigational Site Muenchen Bayern Germany 80339
121 GSK Investigational Site Muenchen Bayern Germany 80809
122 GSK Investigational Site Vilshofen Bayern Germany 94474
123 GSK Investigational Site Wallerfing Bayern Germany 94574
124 GSK Investigational Site Angermuende Brandenburg Germany 16278
125 GSK Investigational Site Elsterwerda Brandenburg Germany 04910
126 GSK Investigational Site Potsdam Brandenburg Germany 14469
127 GSK Investigational Site Grossalmerode Hessen Germany 37247
128 GSK Investigational Site Kelkheim Hessen Germany 65779
129 GSK Investigational Site Winsen/Lohe Niedersachsen Germany 21423
130 GSK Investigational Site Bad Oeynhausen Nordrhein-Westfalen Germany 32545
131 GSK Investigational Site Bergkamen Nordrhein-Westfalen Germany 59192
132 GSK Investigational Site Dorsten Nordrhein-Westfalen Germany 46282
133 GSK Investigational Site Eschweiler Nordrhein-Westfalen Germany 52249
134 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45329
135 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45355
136 GSK Investigational Site Goch Nordrhein-Westfalen Germany 47574
137 GSK Investigational Site Koeln Nordrhein-Westfalen Germany 50823
138 GSK Investigational Site Koeln Nordrhein-Westfalen Germany 51069
139 GSK Investigational Site Witten Nordrhein-Westfalen Germany 58455
140 GSK Investigational Site Ingelheim Rheinland-Pfalz Germany 55218
141 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55116
142 GSK Investigational Site Rhaunen Rheinland-Pfalz Germany 55624
143 GSK Investigational Site Neunkirchen Saarland Germany 66539
144 GSK Investigational Site Koethen Sachsen-Anhalt Germany 06366
145 GSK Investigational Site Schoenebeck Sachsen-Anhalt Germany 39218
146 GSK Investigational Site Wolmirstedt Sachsen-Anhalt Germany 39326
147 GSK Investigational Site Zerbst Sachsen-Anhalt Germany 39261
148 GSK Investigational Site Borna Sachsen Germany 04552
149 GSK Investigational Site Delitzsch Sachsen Germany 04509
150 GSK Investigational Site Dresden Sachsen Germany 01099
151 GSK Investigational Site Dresden Sachsen Germany 01307
152 GSK Investigational Site Leipzg Sachsen Germany 04109
153 GSK Investigational Site Leipzig Sachsen Germany 04103
154 GSK Investigational Site Oschatz Sachsen Germany 04758
155 GSK Investigational Site Pirna Sachsen Germany 01796
156 GSK Investigational Site Berlin Germany 10367
157 GSK Investigational Site Berlin Germany 10629
158 GSK Investigational Site Berlin Germany 10787
159 GSK Investigational Site Berlin Germany 13125
160 GSK Investigational Site Berlin Germany 13158
161 GSK Investigational Site Hamburg Germany 22177
162 GSK Investigational Site Ahmedabad India 380006
163 GSK Investigational Site Bangalore India 560 010
164 GSK Investigational Site Bangalore India 560034
165 GSK Investigational Site Banjara Hills PO, Hyderabad India 500 034
166 GSK Investigational Site Belgaum India 590001
167 GSK Investigational Site Chennai India 600 008
168 GSK Investigational Site Chennai India 600 028
169 GSK Investigational Site Cochin India 683572
170 GSK Investigational Site Hyderabad India 500034
171 GSK Investigational Site Karnal India 132001
172 GSK Investigational Site Kerala India 688 524
173 GSK Investigational Site Kochi India 682 040
174 GSK Investigational Site Kochi India 682026
175 GSK Investigational Site Kottyam India 686 027
176 GSK Investigational Site Mumbai India 400007
177 GSK Investigational Site Nasik India 422013
178 GSK Investigational Site Nellore India 524001
179 GSK Investigational Site Pune India 411004
180 GSK Investigational Site Tamil Nadu India Trichy - 620 018
181 GSK Investigational Site Trivandrum India 695607
182 GSK Investigational Site Vijayawada India 520008
183 GSK Investigational Site Milano (Milan) Lombardia Italy 20132
184 GSK Investigational Site Sesto San Giovanni (MI) Lombardia Italy 20099
185 GSK Investigational Site Pozzilli (IS) Molise Italy 86077
186 GSK Investigational Site Chieri (Torino) Italy 10023
187 GSK Investigational Site Cesis Latvia LV4100
188 GSK Investigational Site Daugavpils Latvia LV5417
189 GSK Investigational Site Jekabpils Latvia LV5201
190 GSK Investigational Site Liepaja Latvia LV3401
191 GSK Investigational Site Riga Latvia LV 1002
192 GSK Investigational Site Riga Latvia LV 1011
193 GSK Investigational Site Riga Latvia LV1024
194 GSK Investigational Site Tukums Latvia LV 3100
195 GSK Investigational Site Tijuana Baja California Norte Mexico 22010
196 GSK Investigational Site Guadalajara Jalisco Mexico 44150
197 GSK Investigational Site Guadalajara Jalisco Mexico 44380
198 GSK Investigational Site Guadalajara Jalisco Mexico 44600
199 GSK Investigational Site Guadalajara Jalisco Mexico CP 44340
200 GSK Investigational Site Zapopan Jalisco Mexico 45200
201 GSK Investigational Site Morelia Michoacán Mexico
202 GSK Investigational Site San Luis Potosi San Luis Potosí Mexico 78200
203 GSK Investigational Site Aguascalientes Mexico 20230
204 GSK Investigational Site Guadalajara Mexico
205 GSK Investigational Site Tampico Mexico
206 GSK Investigational Site Amsterdam Netherlands 1061 AE
207 GSK Investigational Site Heerlen Netherlands 6419 PC
208 GSK Investigational Site Hoofddorp Netherlands 2134
209 GSK Investigational Site Rotterdam Netherlands 3015 CE
210 GSK Investigational Site Rotterdam Netherlands 3045 PM
211 GSK Investigational Site Bodø Norway 8005
212 GSK Investigational Site Hoenefoss Norway 3513
213 GSK Investigational Site Kløfta Norway 2040
214 GSK Investigational Site Oslo Norway 0160
215 GSK Investigational Site Oslo Norway 0319
216 GSK Investigational Site Oslo Norway 0514
217 GSK Investigational Site Skedsmokorset Norway N-2020
218 GSK Investigational Site Stavanger Norway 4005
219 GSK Investigational Site Tromsø Norway 9038
220 GSK Investigational Site Trondheim Norway 7212
221 GSK Investigational Site Faisalabad Pakistan 37250
222 GSK Investigational Site Islamabad Pakistan 44000
223 GSK Investigational Site Lahore Pakistan 54000
224 GSK Investigational Site Arequipa Peru 54
225 GSK Investigational Site Laoag City Philippines 2900
226 GSK Investigational Site Bacau Romania 600114
227 GSK Investigational Site Baia Mare Romania 435400
228 GSK Investigational Site Bistrita Romania 420016
229 GSK Investigational Site Brasov Romania 500365
230 GSK Investigational Site Bucuresti Romania 020475
231 GSK Investigational Site Buzau Romania 120203
232 GSK Investigational Site Deva Romania 330084
233 GSK Investigational Site Iasi Romania 700547
234 GSK Investigational Site Oradea Romania 410469
235 GSK Investigational Site Pitesti Romania 110084
236 GSK Investigational Site Sibiu Romania 550245
237 GSK Investigational Site Arkhangelsk Russian Federation 163045
238 GSK Investigational Site Barnaul Russian Federation 656 045
239 GSK Investigational Site Barnaul Russian Federation 656038
240 GSK Investigational Site Barnaul Russian Federation 656055
241 GSK Investigational Site Ivanovo Russian Federation 153012
242 GSK Investigational Site Ivanovo Russian Federation 153462
243 GSK Investigational Site Kazan Russian Federation 420012
244 GSK Investigational Site Kazan Russian Federation 420033
245 GSK Investigational Site Kemerovo Russian Federation 650000
246 GSK Investigational Site Kemerovo Russian Federation 650002
247 GSK Investigational Site Kemerovo Russian Federation 650036
248 GSK Investigational Site Kirov Russian Federation 610030
249 GSK Investigational Site Kursk Russian Federation 305035
250 GSK Investigational Site Moscow Russian Federation 111539
251 GSK Investigational Site Moscow Russian Federation 115487
252 GSK Investigational Site Moscow Russian Federation 117 036
253 GSK Investigational Site Moscow Russian Federation 117556
254 GSK Investigational Site Moscow Russian Federation 121 552
255 GSK Investigational Site Moscow Russian Federation 121552
256 GSK Investigational Site Moscow Russian Federation 123448
257 GSK Investigational Site Moscow Russian Federation 125367
258 GSK Investigational Site Moscow Russian Federation 129110
259 GSK Investigational Site Nizhniy Novgorod Russian Federation 603076
260 GSK Investigational Site Nizhniy Novgorod Russian Federation 603126
261 GSK Investigational Site Nizhny Novgorod Russian Federation 603003
262 GSK Investigational Site Ryazan Russian Federation 390026
263 GSK Investigational Site Saint-Petersburg Russian Federation 197341
264 GSK Investigational Site Saint-Petersburg Russian Federation 198260
265 GSK Investigational Site Saratov Russian Federation 410031
266 GSK Investigational Site Smolensk Russian Federation 214 019
267 GSK Investigational Site St Pertersburg Russian Federation 196247
268 GSK Investigational Site St Petersberg Russian Federation 192288
269 GSK Investigational Site St'Petersburg Russian Federation 194156
270 GSK Investigational Site St'Petersburg Russian Federation 197110
271 GSK Investigational Site St-Petersburg Russian Federation 193312
272 GSK Investigational Site St-Petersburg Russian Federation 194017
273 GSK Investigational Site St-Petersburg Russian Federation 195067
274 GSK Investigational Site St-Petersburg Russian Federation 195197
275 GSK Investigational Site St. Petersburg Russian Federation 197758
276 GSK Investigational Site St. Petersburg Russian Federation 198205
277 GSK Investigational Site Syktyvkar Russian Federation 167 981
278 GSK Investigational Site Tomsk Russian Federation 634012
279 GSK Investigational Site Tomsk Russian Federation 634050
280 GSK Investigational Site Tomsk Russian Federation 634063
281 GSK Investigational Site Vladivostok Russian Federation 690034
282 GSK Investigational Site Vladivostok Russian Federation 690105
283 GSK Investigational Site Volgograd Russian Federation 400008
284 GSK Investigational Site Voronezh Russian Federation 394018
285 GSK Investigational Site Yaroslavl Russian Federation 150003
286 GSK Investigational Site Bratislava Slovakia 826 06
287 GSK Investigational Site Bratislava Slovakia 831 01
288 GSK Investigational Site Nitra Slovakia 949 11
289 GSK Investigational Site Port Elizabeth Eastern Cape South Africa 6014
290 GSK Investigational Site Meyerspark Gauteng South Africa 0184
291 GSK Investigational Site Parktown Gauteng South Africa 2193
292 GSK Investigational Site Chatsworth KwaZulu- Natal South Africa 4092
293 GSK Investigational Site Umhlanga Rocks KwaZulu- Natal South Africa 4320
294 GSK Investigational Site Bellville South Africa 7531
295 GSK Investigational Site Benoni South Africa 1501
296 GSK Investigational Site Bloemfontein South Africa 9301
297 GSK Investigational Site Cape Town South Africa 7500
298 GSK Investigational Site Cape Town South Africa 7800
299 GSK Investigational Site Durban South Africa 4001
300 GSK Investigational Site Newton South Africa 2113
301 GSK Investigational Site Observatory South Africa 7925
302 GSK Investigational Site Parktown South Africa 2193
303 GSK Investigational Site Pretoria South Africa 0002
304 GSK Investigational Site Somerset West South Africa 7130
305 GSK Investigational Site Soweto South Africa 1111
306 GSK Investigational Site Soweto South Africa 2013
307 GSK Investigational Site Worcester South Africa 6850
308 GSK Investigational Site Eksjö Sweden SE-575 36
309 GSK Investigational Site Göteborg Sweden SE-413 45
310 GSK Investigational Site Göteborg Sweden SE-416 85
311 GSK Investigational Site Göteborg Sweden SE-417 17
312 GSK Investigational Site Härnösand Sweden SE-871 82
313 GSK Investigational Site Karlshamn Sweden SE-374 80
314 GSK Investigational Site Kristianstad Sweden SE-291 85
315 GSK Investigational Site Ljungby Sweden SE-341 82
316 GSK Investigational Site Malmö Sweden SE-205 02
317 GSK Investigational Site Malmö Sweden SE-214 22
318 GSK Investigational Site Oskarshamn Sweden SE-572 28
319 GSK Investigational Site Skene Sweden SE-511 62
320 GSK Investigational Site Stockholm Sweden SE-111 57
321 GSK Investigational Site Stockholm Sweden SE-171 76
322 GSK Investigational Site Vällingby Sweden SE-162 68
323 GSK Investigational Site Växjö Sweden SE-351 85
324 GSK Investigational Site Bangkok Thailand 10400
325 GSK Investigational Site Bath Somerset United Kingdom BA1 3NG
326 GSK Investigational Site Chippenham United Kingdom SN15 2SB
327 GSK Investigational Site Doncaster United Kingdom DN9 1EP
328 GSK Investigational Site Harrogate United Kingdom HG1 5JP
329 GSK Investigational Site London United Kingdom E1 1BB
330 GSK Investigational Site Manchester United Kingdom M13 9Wl
331 GSK Investigational Site Sheffield United Kingdom S10 2RX

Sponsors and Collaborators

  • GlaxoSmithKline
  • Population Health Research Institute

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00879970
Other Study ID Numbers:
  • 111960
First Posted:
Apr 13, 2009
Last Update Posted:
Apr 18, 2017
Last Verified:
Mar 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Cardiovascular Outcomes
Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Vitamin D
Pioglitazone
Rosiglitazone

Study Results

Participant Flow

Recruitment Details 1332 participants were included in the TZD randomization, and 1221 of 1332 participants were included in the Vitamin D randomization.
Pre-assignment Detail Randomization occurred subsequent to a 3-week rosiglitazone (RSG) and vitamin D Single-blind Run-in Phase to assess compliance and tolerability. Participants received an RSG tablet (4 milligrams [mg]) and a vitamin D tablet (1000 international units [IU]) once a day.
Arm/Group Title Placebo Pioglitazone (PIO) Rosiglitazone (RSG) Vitamin D Placebo Vitamin D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Period Title: Period 1 TZD Randomization
STARTED 541 392 399 0 0
COMPLETED 533 388 393 0 0
NOT COMPLETED 8 4 6 0 0
Period Title: Period 1 TZD Randomization
STARTED 0 0 0 614 607
COMPLETED 0 0 0 610 600
NOT COMPLETED 0 0 0 4 7

Baseline Characteristics

Arm/Group Title Placebo Pioglitazone (PIO) Rosiglitazone (RSG) Total
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Total of all reporting groups
Overall Participants 541 392 399 1332
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
66.4
(6.8)
66.3
(6.6)
66.5
(6.4)
66.4
(6.6)
Sex: Female, Male (Count of Participants)
Female
220
40.7%
167
42.6%
161
40.4%
548
41.1%
Male
321
59.3%
225
57.4%
238
59.6%
784
58.9%
Race/Ethnicity, Customized (participants) [Number]
European/ Caucasian/ White
330
61%
241
61.5%
255
63.9%
826
62%
Unknown
53
9.8%
34
8.7%
35
8.8%
122
9.2%
South Asian
63
11.6%
46
11.7%
48
12%
157
11.8%
Black African
45
8.3%
35
8.9%
26
6.5%
106
8%
Native South American
33
6.1%
26
6.6%
24
6%
83
6.2%
Other Asian
10
1.8%
6
1.5%
6
1.5%
22
1.7%
Native North American
1
0.2%
2
0.5%
4
1%
7
0.5%
Japanese
1
0.2%
0
0%
1
0.3%
2
0.2%
Arab/ Persian
1
0.2%
1
0.3%
0
0%
2
0.2%
Native Hawaiian/ Australian or Other Asian Pacific
1
0.2%
1
0.3%
0
0%
2
0.2%
Malays
1
0.2%
0
0%
0
0%
1
0.1%
Sub-Saharan African
1
0.2%
0
0%
0
0%
1
0.1%
Missing
1
0.2%
0
0%
0
0%
1
0.1%

Outcome Measures

1. Primary Outcome
Title Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)
Description 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).
Time Frame From Randomization at Visit 3 up to the Final Visit (average of 162 days)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants
Arm/Group Title Placebo Pioglitazone (PIO) Rosiglitazone (RSG) Vitamin D Placebo Vitamin D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
CV Death/Non-Fatal MI/Non-Fatal Stroke
5
0.9%
2
0.5%
1
0.3%
3
0.2%
2
NaN
CV Death
1
0.2%
0
0%
0
0%
1
0.1%
0
NaN
Non-Fatal MI
2
0.4%
0
0%
1
0.3%
1
0.1%
1
NaN
Non-Fatal Stroke
2
0.4%
2
0.5%
0
0%
1
0.1%
1
NaN
2. Primary Outcome
Title Number of Participants With the Indicated Components of the Composite Outcome for Vitamin D
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitzaone Rosiglitazone Vitamin D Placebo Vitamin D
Arm/Group Description PLACEBO Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Death or serious cancer
6
1.1%
3
0.8%
1
0.3%
3
0.2%
2
NaN
All death
4
0.7%
1
0.3%
1
0.3%
2
0.2%
0
NaN
Serious cancer
2
0.4%
2
0.5%
0
0%
1
0.1%
2
NaN
3. Secondary Outcome
Title Number of Participants With Any Revascularization
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
6
1.1%
3
0.8%
5
1.3%
7
0.5%
5
NaN
4. Secondary Outcome
Title Number of Participants With Need for Hospitalization for Any Reason
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
31
5.7%
16
4.1%
24
6%
19
1.4%
32
NaN
5. Secondary Outcome
Title Number of Participants With Need for Hospitalization for Congestive Heart Failure (CHF), Shortness of Breath, Pneumonia, or Angina
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
CHF
1
0.2%
2
0.5%
0
0%
0
0%
2
NaN
Shortness of breath
0
0%
1
0.3%
2
0.5%
0
0%
1
NaN
Pneumonia
0
0%
1
0.3%
0
0%
0
0%
0
NaN
Angina
3
0.6%
1
0.3%
1
0.3%
NA
NaN
NA
NaN
6. Secondary Outcome
Title Number of Participants With Composite Microvascular Outcome
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
21
3.9%
8
2%
9
2.3%
18
1.4%
18
NaN
7. Secondary Outcome
Title Number of Participants With Retinopathy Requiring Laser Therapy, a Decline in Estimated Glomerular Filtration Rate (eGFR), Vitrectomy, and Renal Replacement Therapy
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Retinopathy Requiring Laser Therapy
1
0.2%
0
0%
0
0%
0
0%
0
NaN
Decline in eGFR >=30%
20
3.7%
8
2%
9
2.3%
18
1.4%
18
NaN
Vitrectomy
0
0%
0
0%
0
0%
0
0%
0
NaN
Renal Replacement Therapy
0
0%
0
0%
0
0%
0
0%
0
NaN
8. Secondary Outcome
Title Number of Participants With Severe Lower Than Normal Blood Glucose Level (Hypoglycemia)
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
0
0%
2
0.5%
1
0.3%
0
0%
3
NaN
9. Secondary Outcome
Title Number of Participants With Clinical Proteinuria
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
1
0.2%
0
0%
0
0%
NA
NaN
NA
NaN
10. Secondary Outcome
Title Number of Participants With a Fracture
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
2
0.4%
2
0.5%
3
0.8%
3
0.2%
3
NaN
11. Secondary Outcome
Title Number of Participants With Hepatic Enzyme Increased or Abnormal Liver Function Tests
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 541 392 399 614 607
Number [participants]
1
0.2%
0
0%
1
0.3%
NA
NaN
NA
NaN
12. Secondary Outcome
Title Number of Participants With Cognitive (Mental Processes) Decline (CD) From Baseline to the Year 2 Visit and the Final Visit
Description 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).
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population. Study participation was placed on full clinical hold before data could be collected for this endpoint.
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 0 0 0 0 0
13. Secondary Outcome
Title Number of Participants With Erectile Dysfunction
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population. Study participation was placed on full clinical hold before data could be collected for this endpoint.
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 0 0 0 0 0
14. Secondary Outcome
Title Mean Score on Euro-QoL (EQ)-5D
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population. Study participation was placed on full clinical hold before data could be collected for this endpoint.
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 0 0 0 0 0
15. Secondary Outcome
Title Mean Score on Montreal Cognitive Assessment (MoCA) Test, as an Assessment of Cognitive Function (CF)
Description 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.
Time Frame From Randomization at Visit 3 to Final Visit (up to 162 days)

Outcome Measure Data

Analysis Population Description
ITT Population. Study participation was placed on full clinical hold before data could be collected for this endpoint.
Arm/Group Title Placebo Pioglitazone Rosiglitazone VITAMIN D PLACEBO VITAMIN D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days. 1,000 IU/day administered for a mean duration of 162 days.
Measure Participants 0 0 0 0 0

Adverse Events

Time Frame 162 days for the TZD arm; 130 days for the vitamin D arm
Adverse Event Reporting Description Non-serious AE's were not analyzed including the Vitamin D Placebo and Vitamin D arms. As a result, data is presented as "0" participants at risk for both the Vitamin D Placebo and Vitamin D arms.
Arm/Group Title Placebo Pioglitazone Rosiglitazone Vitamin D Placebo Vitamin D
Arm/Group Description Matching placebo tablet was administered once a day (OD) for a mean duration of 162 days. PIO tablet was administered in the dose of 30-45 milligrams (mg) OD for a mean duration of 162 days. RSG tablet was administered in the dose of 4-8 mg OD for a mean duration of 162 days. Vitamin D placebo administered for a mean duration of 162 days 1,000 IU/day administered for a mean duration of 162 days.
All Cause Mortality
Placebo Pioglitazone Rosiglitazone Vitamin D Placebo Vitamin D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Placebo Pioglitazone Rosiglitazone Vitamin D Placebo Vitamin D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/541 (1.3%) 5/392 (1.3%) 2/399 (0.5%) 2/614 (0.3%) 9/607 (1.5%)
Gastrointestinal disorders
Intestinal prolapse 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
General disorders
Multi-organ failure 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 0/607 (0%)
Hepatobiliary disorders
Cholecystitis acute 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/614 (0%) 0/607 (0%)
Infections and infestations
Chronic sinusitis 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Metabolism and nutrition disorders
Hypoglycemia 0/541 (0%) 1/392 (0.3%) 1/399 (0.3%) 0/614 (0%) 2/607 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/614 (0%) 0/607 (0%)
Renal and urinary disorders
Hydronephrosis 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Reproductive system and breast disorders
Benign prostatic hyperplasia 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Respiratory, thoracic and mediastinal disorders
Bronchial disorder 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 1/614 (0.2%) 0/607 (0%)
Chronic obstructive pulmonary disease 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Skin and subcutaneous tissue disorders
Pruritis allergic 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Surgical and medical procedures
Angioplasty 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 1/607 (0.2%)
Aortic aneurysm repair 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 1/614 (0.2%) 0/607 (0%)
Vascular disorders
Aortic aneurysm 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/614 (0%) 0/607 (0%)
Other (Not Including Serious) Adverse Events
Placebo Pioglitazone Rosiglitazone Vitamin D Placebo Vitamin D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 36/541 (6.7%) 35/392 (8.9%) 21/399 (5.3%) 0/0 (NaN) 0/0 (NaN)
Cardiac disorders
Angina pectoris 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Cardiac failure 3/541 (0.6%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Myocardial infarction 1/541 (0.2%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Palpitations 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Right ventricular failure 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Tachycardia 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Ventricular tachycardia 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Ear and labyrinth disorders
Vertigo 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Eye disorders
Vision blurred 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Gastrointestinal disorders
Abdominal discomfort 1/541 (0.2%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Abdominal distension 0/541 (0%) 0/392 (0%) 2/399 (0.5%) 0/0 (NaN) 0/0 (NaN)
Abdominal pain 1/541 (0.2%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Abdominal pain upper 0/541 (0%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Constipation 0/541 (0%) 3/392 (0.8%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Crohn's disease 1/541 (0.2%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Diarrhea 2/541 (0.4%) 3/392 (0.8%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Dry mouth 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Dyspepsia 1/541 (0.2%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Dysphagia 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Flatulence 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Nausea 2/541 (0.4%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Peptic ulcer 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Vomiting 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
General disorders
Asthenia 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Chest pain 1/541 (0.2%) 0/392 (0%) 2/399 (0.5%) 0/0 (NaN) 0/0 (NaN)
Drug intolerance 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Fatigue 0/541 (0%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Malaise 1/541 (0.2%) 3/392 (0.8%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Edema 2/541 (0.4%) 5/392 (1.3%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Edema peripheral 4/541 (0.7%) 8/392 (2%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Swelling 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Temperature intolerance 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Infections and infestations
Urinary tract infection 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Investigations
Cardiac stress test abnormal 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Catheterisation cardiac 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Echocardiogram abnormal 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Ejection fraction abnormal 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Ejection fraction decreased 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Electrocardiogram abnormal 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Electrocardiogram change 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Glycosylated hemoglobin increased 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Hepatic enzyme increased 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Liver function test abnormal 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Weight increased 0/541 (0%) 2/392 (0.5%) 2/399 (0.5%) 0/0 (NaN) 0/0 (NaN)
Metabolism and nutrition disorders
Decreased appetite 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Diabetes mellitus inadequate control 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Fluid overload 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Fluid retention 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Hypoglycemia 1/541 (0.2%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Musculoskeletal and connective tissue disorders
Joint swelling 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Muscle spasms 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Musculoskeletal pain 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Myalgia 0/541 (0%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Osteoarthritis 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Osteoporosis 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Pain in extremity 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Neoplasm malignant 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Nervous system disorders
Renal cancer 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Cerebrovascular accident 1/541 (0.2%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Dizziness 0/541 (0%) 2/392 (0.5%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Syncope 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Renal and urinary disorders
Bladder obstruction 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Chromaturia 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Hydronephrosis 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Dyspnea 1/541 (0.2%) 3/392 (0.8%) 4/399 (1%) 0/0 (NaN) 0/0 (NaN)
Sinus disorder 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Skin and subcutaneous tissue disorders
Erythema 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Hyperhidrosis 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Rash pruritic 0/541 (0%) 1/392 (0.3%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Skin discoloration 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Surgical and medical procedures
Cardiac pacemaker insertion 0/541 (0%) 0/392 (0%) 1/399 (0.3%) 0/0 (NaN) 0/0 (NaN)
Hospitalization 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)
Surgery 1/541 (0.2%) 0/392 (0%) 0/399 (0%) 0/0 (NaN) 0/0 (NaN)

Limitations/Caveats

The intended duration of this study was approximately 5.5 years. However, the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00879970
Other Study ID Numbers:
  • 111960
First Posted:
Apr 13, 2009
Last Update Posted:
Apr 18, 2017
Last Verified:
Mar 1, 2017