PROactive: Study design

1
PROactive Study design
Objective Assess the effects of pioglitazone
on reducing macrovascular events in type 2
diabetes Design Randomized, double-blind,
placebo-controlled Population N 5238 with
type 2 diabetes and history of macrovascular
disease Treatment Pioglitazone (up to 45 mg)
or placebo Primary outcome Composite of
all-cause mortality, MI, ACS, coronary or
peripheral revascularization, amputation,
stroke Secondary outcomes Individual
components of primary outcome, CV
mortality Follow-up 4 years
Dormandy JA et al. Lancet. 20053661279-89. Charb
onnel B et al. Diabetes Care. 2004271647-53.
2
PROactive Baseline characteristics
Patient description Mean SD Age (yrs) 61.8
7.7 Male () 66.1 Caucasian () 98.5 Type 2
diabetes (yrs since onset) 9.5 7.0 Weight
(lbs) 194 34 BMI (kg/m2) 30.9 4.8 Waist
circumference (in) 41.46 4.7 Systolic BP (mm
Hg) 143.4 17.8 Triglycerides (mg/dL) 198.4
158.8 HDL-C (mg/dL) 44.9 12 LDL-C (mg/dL) 114.5
37 A1C () 8.08 1.41
Charbonnel B et al. Diabetes Care.
2004271647-53.
3
PROactive CV medications at study entry
Current therapy n ()
?-Blockers 2859 (55) ACEI 3286 (63) ARB 356 (7)
CCB 1855 (35) Nitrates 2058 (39) Thiazide 830 (
16) Antiplatelets 4394 (84)
Aspirin 3829 (73) Statins 2135 (41) Fibrates 448
(9)
Charbonnel B et al. Diabetes Care.
2004271647-53.
4
PROactive Reduction in primary outcome
All-cause mortality, nonfatal MI (including
silent MI), ACS, revascularization, leg
amputation, stroke
25
10 RRR HR 0.90 (0.801.02)P 0.095
Placebo(572 events)
20
Pioglitazone(514 events)
15
Proportionof events()
10
5
0
6
0
12
18
24
30
36
Time from randomization (months)
Number at risk
Pioglitazone
2488
2373
2302
2218
2146
348
Placebo
2530
2413
2317
2215
2122
345
Dormandy JA et al. Lancet. 20053661279-89.
Unadjusted
5
PROactive Reduction in secondary outcome
Combined nonfatal MI, all-cause mortality, stroke
25
20
Placebo(358 events)
16 RRR HR 0.84 (0.720.98)P 0.027
15
Proportionof events()
10
Pioglitazone(301 events)
5
0
6
0
12
18
24
30
36
Time from randomization (months)
Number at risk
Pioglitazone
2536
2487
2435
2381
2336
396
Placebo
2566
2504
2442
2371
2315
390
Dormandy JA et al. Lancet. 20053661279-89.
Unadjusted
6
PROactive Reduced need for insulin
25
Placebo(362 events)
20
53 RRR HR 0.47 (0.390.56)P lt 0.0001
15
Proportionof events()
10
Pioglitazone(183 events)
5
0
6
0
12
18
24
30
36
Time from randomization (months)
Number at risk
Pioglitazone
1700
1654
1603
1554
1499
244
Placebo
1646
1544
1472
1401
1325
202
Dormandy JA et al. Lancet. 20053661279-89.
Unadjusted