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Intensive Glycemic Control and Skeletal Health Study (ACCORD-BONE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00324350
Recruitment Status : Completed
First Posted : May 11, 2006
Results First Posted : October 5, 2012
Last Update Posted : October 5, 2012
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of California, San Francisco

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Single (Investigator);   Primary Purpose: Prevention
Conditions Atherosclerosis
Cardiovascular Diseases
Hypercholesterolemia
Hypertension
Diabetes Mellitus
Coronary Disease
Intervention Drug: hypoglycemic agents, hydroxymethylglutaryl-CoA Reductase inhibitors, hypertensive agents
Enrollment 7287
Recruitment Details The ACCORD trial has been described previously (Buse JB,et al. Am J Cardiol 99:21i-33i, 2007). Five of the 7 clinical center networks agreed to participate in the BONE ancillary study, including 54 of 77 clinical sites and 7,287 participants. The BONE ancillary study was initiated during the main recruitment for ACCORD (beginning in 2006).
Pre-assignment Details  
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control
Hide Arm/Group Description intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
Period Title: Overall Study
Started 3655 3632
Non-Vertebral Fracture Follow-Up 3655 3632
Falls Follow-Up 3364 3418
Completed 3655 3632
Not Completed 0 0
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control Total
Hide Arm/Group Description intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors Total of all reporting groups
Overall Number of Baseline Participants 3655 3632 7287
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3655 participants 3632 participants 7287 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2380
  65.1%
2361
  65.0%
4741
  65.1%
>=65 years
1275
  34.9%
1271
  35.0%
2546
  34.9%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3655 participants 3632 participants 7287 participants
62.5  (6.7) 62.6  (6.7) 62.5  (6.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3655 participants 3632 participants 7287 participants
Female
1267
  34.7%
1251
  34.4%
2518
  34.6%
Male
2388
  65.3%
2381
  65.6%
4769
  65.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3655 participants 3632 participants 7287 participants
United States 2903 2876 5779
Canada 752 756 1508
1.Primary Outcome
Title Number of Participants With at Least One Non-vertebral Fracture
Hide Description The BONE ancillary study was initiated during recruitment for the main ACCORD trial. Beginning in January 2006, at the next annual visit participants were asked about the occurrence of any non-spine fractures since randomization. After the annual visit in 2006, participants were asked if they had suffered a fracture since their last annual visit. Reported fracture events were centrally adjudicated, based on radiology records, at the University of California, San Francisco (UCSF) with the adjudicators blinded to treatment assignment.
Time Frame Average follow-up of 3.8 years
Hide Outcome Measure Data
Hide Analysis Population Description
As per protocol, pathological fractures, confirmed as occurring secondary to neoplasm, necrosis, or sepsis, and periprosthetic fractures were excluded (N=7). These analyses are limited to confirmed fractures that occurred on or before Feb 5, 2008, when the intensive glycemia intervention was ended.
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control
Hide Arm/Group Description:
intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
Overall Number of Participants Analyzed 3655 3632
Measure Type: Number
Unit of Measure: participants
198 189
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intensive Glycemic Control, Standard Glycemic Control
Comments The BONE ancillary study was designed to have 80% power to detect a relative reduction in risk of non-spine clinical fractures of 22-29%. This was based on an estimated total number of fractures between 259-494, calculated with the following assumptions: rate of clinical non-spine fracture among women in the standard glycemia therapy group between 15 and 25/1000 person yrs, fracture rates for men between 35-40% of the rates for women of the same age, and an avg follow-up time of 4.6 yrs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.678
Comments Analyses were by intention to treat. All analyses adjusted for baseline cardiovascular disease, assignment to blood pressure (BP) trial or lipid trial, assignment to intensive BP intervention in BP trial, and assignment to fibrate in lipid trial.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.86 to 1.27
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With at Least One Fall
Hide Description At each annual visit starting in January 2006, participants were also asked about falling: "In the last 12 months have you fallen and landed on the floor or ground, OR fallen and hit an object like a table or stair?" Those who answered "yes" were also asked how many times they had fallen in the previous 12 months.
Time Frame Average follow-up of 2.0 years
Hide Outcome Measure Data
Hide Analysis Population Description
These analyses include results from the annual visits that occurred before Feb 5, 2008, the close of the intensive glycemia arm. Of those in the BONE ancillary study, 6,782 participants answered at least one question about falls.
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control
Hide Arm/Group Description:
intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%) in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
Overall Number of Participants Analyzed 3364 3418
Measure Type: Number
Unit of Measure: participants
1122 1133
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intensive Glycemic Control, Standard Glycemic Control
Comments Number of participants with falls reported at each annual visit were compared by treatment assignment using a repeated-measures negative binomial model, with robust standard errors to account for clustering of the repeated outcomes within participants; the log of the length of the reporting period varied slightly and was included as an offset
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.490
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.84 to 1.43
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With > 2 cm of Height Loss
Hide Description Standing height was measured according to a standard protocol at baseline and annual visits on all ACCORD participants. Height loss was compared by treatment assignment using linear mixed models with random intercepts and slopes. Treatment effects were captured by the interaction between treatment assignment and time. The proportions losing >2 cm of height during follow-up were compared using logistic models. This degree of height loss is associated with incident vertebral fracture with 94% specificity but only 28% sensitivity
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Among participants in the BONE ancillary study, 6,979 participants had at least one height measurement during follow-up and were included in these analyses.
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control
Hide Arm/Group Description:
intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
Overall Number of Participants Analyzed 3482 3497
Measure Type: Number
Unit of Measure: participants
678 686
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intensive Glycemic Control, Standard Glycemic Control
Comments Height loss was compared by treatment assignment using linear mixed models with random intercepts and slopes. The proportions losing >2 cm of height during follow-up were compared using logistic models. Based on previous research by Siminoski et al., this degree of height loss is associated with incident vertebral fracture with 94% specificity but only 28% sensitivity.(Siminoski K, Jiang G, Adachi JD, et al. Osteoporos Int 2005;16:403–410)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.854
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.88 to 1.11
Estimation Comments The rate of height loss did not differ between groups (p = 0.573). Height loss of >2 cm during ACCORD was experienced by 678 (19.5%) participants in the intensive and 686 (19.6%) in the standard glycemia group (OR 0.99; 95% CI 0.88, 1.11).
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events were not collected as a part of this ACCORD-BONE ancillary study. Please refer to the ACCORD main study results for all adverse event results.
 
Arm/Group Title Intensive Glycemic Control Standard Glycemic Control
Hide Arm/Group Description intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors
All-Cause Mortality
Intensive Glycemic Control Standard Glycemic Control
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Intensive Glycemic Control Standard Glycemic Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Intensive Glycemic Control Standard Glycemic Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
The initial identification of a possible fracture event relied on self-report at annual visits with the possibility of under- or over-reporting of fractures.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Ann Schwartz
Organization: University of California, San Francisco
Phone: 415-514-8000
EMail: aschwartz@psg.ucsf.edu
Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00324350    
Other Study ID Numbers: R01DK069514 ( U.S. NIH Grant/Contract )
First Submitted: May 10, 2006
First Posted: May 11, 2006
Results First Submitted: March 15, 2012
Results First Posted: October 5, 2012
Last Update Posted: October 5, 2012