Meta-Analysis of Amputation Events from Clinical Trials DIA3008 (CANVAS), DIA4003 (CANVAS-R), and DNE3001 (CREDENCE)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Other
• If ‘other’, further details on the scope of the study:
  Meta-Analysis of Amputation Events from Clinical Trials DIA3008 (CANVAS), DIA4003 (CANVAS-R), and DNE3001 (CREDENCE)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Systematic review and meta-analysis

Study drug and medical condition

• Medical condition to be studied:
  Amputation

Population studied

• Short description of the study population:
  Canagliflozin- or placebo-treated subjects in the 3 completed outcome trials (CANVAS, CANVAS-R, and CREDENCE) were evaluated. The patient population of CANVAS and CANVAS-R was subjects with T2DM and either CV disease (secondary prevention) or at least 2 risk factors for a CV event (primary prevention). The patient population of CREDENCE were subjects with T2DM, Stage 2 or 3 chronic kidney disease, and macroalbuminuria, who were receiving standard of care therapy including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Diabetes mellitus patients
• Estimated number of subjects:
  14531

Study design details

• Main study objective:
  To estimate the risk for lower limb amputation in various patient populations in a meta-analysis pooled across the CANVAS, CANVAS-R, and CREDENCE studies.
• Outcomes:
  To estimate the relative risk of the time to first occurrence of lower limb amputation for canagliflozin relative to placebo (ie, hazard ratio and 95% confidence interval) in the various patient populations in a meta-analysis pooled across the CANVAS, CANVAS-R, and CREDENCE studies. To evaluate the risks of preceding adverse events of interest that potentially led to amputation in different study groups (canagliflozin compared with placebo), including an analysis of risk factors defined by patient in subgroups of patients.
• Data analysis plan:
  The analysis sets defined for this meta-analysis of lower limb amputation in terms of the following two components: (1) analysis population, which specifies the subjects included in the analysis, (2) data period, defining the time window during which data will be included in the analysis. In both the On-Study and On-Treatment analysis sets (which include treated subjects with different time windows as detailed below), Day 1 is the first double blind dose date for each subject. If missing or incomplete, the first dose date will be imputed as the randomization date. The primary meta-analyses of lower limb amputation will be based on the On-Study analysis set, selected analyses may also be provided for the On-Treatment analysis set.Analysis Set: On-Treatment/ On-Study. Population: Treated subjects/ Treated subjects. Data Period: Day 1 to the last dose date plus 30 days or the last trial contact date, whichever is earlier/ Day 1 to the last trial contact date up to Global Trial End Date.

Documents

Study results

CSR Synopsis_28431754NAP4001_EUPAS29875