Type 2 Diabetes Mellitus
Conditions
Keywords
Risk of cardiovascular disease and death in patients with type 2 diabetes mellitus
Brief summary
The purpose of this study is to determine whether saxagliptin can reduce the risk of cardiovascular events when used alone or added to other diabetes medications
Detailed description
A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IV Trial to Evaluate the Effect of Saxagliptin on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischaemic Stroke in Patients with Type 2 Diabetes
Interventions
DRUGSaxagliptin
5 mg or 2.5 mg once daily
DRUGPlacebo
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus * HbA1c ≥6.5%. (based on the last measured and documented laboratory measurement within 6 months) * High risk for CV events -Established cardiovascular disease and/or multiple risk factors
Exclusion criteria
* Current or previous (within 6 months) treatment with DPP4 inhibitors and/or GLP-1 mimetics * Acute vascular event \<2months prior to randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke | Randomization (day 0) up to 2.9 years | Participants with CV death, non-fatal MI or non-fatal ischaemic stroke. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation | Randomization (day 0) up to 2.9 years | Participants with CV death, non-fatal MI, non-fatal ischaemic stroke, hospitalisation for heart failure, hospitalisation for unstable angina pectoris, or hospitalisation for coronary revascularisation. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later. |
| Participants With Event of Death | Randomization (day 0) up to 2.9 years | Participants with event of death. If no event, censoring occurs at the patient withdrawal of consent, or last contact -whichever was later. |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Czechia, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Puerto Rico, Russia, South Africa, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
The first participant was enrolled on 10 May 2010 and the last participant completed the study on 16 May 2013. A total of 18206 subjects were enrolled in the study of which 16492 were randomised. Study participants were randomized from 790 centers in 26 countries.
Pre-assignment details
Subjects meeting all inclusion criteria and with no exclusion criteria were randomised in a 1:1 ratio to receive either saxagliptin or matching placebo (Day 0).
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin 5 mg once daily in subjects with normal renal function or mild impaired renal function (eGFR \>50 mL/min); 2.5 mg once daily in subjects with moderate to severe renal impairment (eGFR ≤50 mL/min). | 8,280 |
| Placebo Matching Placebo | 8,212 |
| Total | 16,492 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative withdrawal of consent | 7 | 5 |
| Overall Study | Lost to Follow-up | 15 | 13 |
| Overall Study | Withdrawal by Subject | 180 | 196 |
Baseline characteristics
| Characteristic | Saxagliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 8.52 | 65.0 Years STANDARD_DEVIATION 8.58 | 65.0 Years STANDARD_DEVIATION 8.55 |
| Cardiovascular Risk Category: Cardiovascular disease/Multiple risk factors (CVD/MRF) CVD | 6494 Participants | 6465 Participants | 12959 Participants |
| Cardiovascular Risk Category: Cardiovascular disease/Multiple risk factors (CVD/MRF) MRF | 1786 Participants | 1747 Participants | 3533 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1778 Participants | 1763 Participants | 3541 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6502 Participants | 6449 Participants | 12951 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 33 Participants | 51 Participants |
| Race (NIH/OMB) Asian | 896 Participants | 884 Participants | 1780 Participants |
| Race (NIH/OMB) Black or African American | 278 Participants | 290 Participants | 568 Participants |
| Race (NIH/OMB) More than one race | 768 Participants | 758 Participants | 1526 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 11 Participants | 11 Participants | 22 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 68 Participants | 70 Participants | 138 Participants |
| Race (NIH/OMB) White | 6241 Participants | 6166 Participants | 12407 Participants |
| Renal Functione Categor: Normal or Mild impairment/Moderate impairment/Severe impairment Moderate impairment | 1122 Participants | 1118 Participants | 2240 Participants |
| Renal Functione Categor: Normal or Mild impairment/Moderate impairment/Severe impairment Normal or Mild impairment | 6986 Participants | 6930 Participants | 13916 Participants |
| Renal Functione Categor: Normal or Mild impairment/Moderate impairment/Severe impairment Severe impairment | 172 Participants | 164 Participants | 336 Participants |
| Sex: Female, Male Female | 2768 Participants | 2687 Participants | 5455 Participants |
| Sex: Female, Male Male | 5512 Participants | 5525 Participants | 11037 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3,641 / 8,212 | 3,504 / 8,280 |
| serious Total, serious adverse events | 2,075 / 8,212 | 2,114 / 8,280 |
Outcome results
Primary
Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke
Participants with CV death, non-fatal MI or non-fatal ischaemic stroke. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.
Time frame: Randomization (day 0) up to 2.9 years
Population: Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke | 613 participants |
| Placebo | Participants With Any Event From the Composite of Cardiovascular Death (CV Death), Non-fatal Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke | 609 participants |
Secondary
Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation
Participants with CV death, non-fatal MI, non-fatal ischaemic stroke, hospitalisation for heart failure, hospitalisation for unstable angina pectoris, or hospitalisation for coronary revascularisation. If no event, censoring occurs at the patient withdrawal of consent, last contact, or death (when applicable)-whichever was later.
Time frame: Randomization (day 0) up to 2.9 years
Population: Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation | 1059 participants |
| Placebo | Participants With Any Event From the Composite of CV Death, Non-fatal MI, Non-fatal Ischaemic Stroke, Hospitalisation for Heart Failure, Hospitalisation for Unstable Angina Pectoris, or Hospitalisation for Coronary Revascularisation | 1034 participants |
Secondary
Participants With Event of Death
Participants with event of death. If no event, censoring occurs at the patient withdrawal of consent, or last contact -whichever was later.
Time frame: Randomization (day 0) up to 2.9 years
Population: Intention To Treat (ITT) analysis of randomized population. Events were adjudicated by the Clinical Event Adjudication Committee.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Participants With Event of Death | 420 participants |
| Placebo | Participants With Event of Death | 378 participants |