BAART Analysis

Author

Rawlings Lyle

Fisher’s Exact - Arm @ Primary Endpoint (V14)

  • Odds Ratio of Timolol and Wound Healing by Primary Endpoint
Odds.Ratio Confidence.Interval P.Value
Fisher's Exact Test 0.82 0.21 to 3.17 0.77
Chi-Square Test 0.97

Tests - WHR @ Primary Endpoint (V14)

Test Timolol_Mean_WHR Placebo_Mean_WHR P.Value
T-Test 0.020 0.010 0.14
Wilcoxon Test 0.008 0.008 0.51

KM Healing Plots @ Primary Endpoint (V14)

KM Healing Plots @ Secondary Endpoint (V19)

T Test & Wilcoxon Test

Tests evaluating if there was a significant difference between start size and ulcer size at the primary endpoint in each arm.

  • T Test - Evaluating the Mean

  • Wilcoxon Test - Evaluating the Median

Test P.Value
T Tests
Timolol 0.115
Placebo 0.201
Wilcoxon Tests
Timolol 5e-04
Placebo 0.012

Comparing between arms - wound size delta at primary endpoint.

Value Timolol Placebo P.Value
T - Test Mean 1.03 0.51 0.30
Wilcoxon Test Median 0.40 0.50 0.61

Chi-Squared and Fisher’s Exact, healing status @ Secondary Endpoint (V19)

  • Odds Ratio: Timolol has an impact on healing at secondary endpoint.
Odds.Ratio Confidence.Interval P.Value
Fisher's Exact Test 0.41 0.1 to 1.51 0.15
Chi-Square Test 0.21

Correlation of Wound Characteristics with Patient Characteristics

Reulceration Fisher’s Exact

  • Odds Ratio: Timolol has an impact on reulceration.
Odds.Ratio Confidence.Interval P.Value
Fisher's Exact Test 0.49 0.04 to 4.72 0.64
Chi-Square Test 0.77

Table 1

Continuous Variables

Overall
(N=48)
Age
Mean (SD) 67.6 (7.65)
Median [Min, Max] 67.0 [50.0, 83.0]
First HgbA1c
Mean (SD) 8.51 (1.36)
Median [Min, Max] 8.20 [5.90, 11.8]
Monofilament Score
Mean (SD) 1.46 (2.55)
Median [Min, Max] 0 [0, 10.0]
Duration of Diabetes
Mean (SD) 18.1 (9.69)
Median [Min, Max] 19.5 [1.00, 51.0]
DFU Severity Score
Mean (SD) 4.33 (2.05)
Median [Min, Max] 3.00 [3.00, 11.0]
ABI
Mean (SD) 1.20 (0.222)
Median [Min, Max] 1.18 [0.830, 2.04]
Missing 8 (16.7%)
Toe Pressure
Mean (SD) 113 (29.5)
Median [Min, Max] 110 [51.0, 196]
Missing 12 (25.0%)
Charlson Comorbidity Index
Mean (SD) 2.67 (0.975)
Median [Min, Max] 2.00 [2.00, 6.00]
Initial Ulcer Age (weeks)
Mean (SD) 24.0 (31.5)
Median [Min, Max] 10.0 [3.00, 165]
Initial Ulcer Size (cm2)
Mean (SD) 1.67 (1.85)
Median [Min, Max] 0.800 [0.300, 9.70]
Days to Primary Endpoint
Mean (SD) 80.5 (26.8)
Median [Min, Max] 91.0 [21.0, 135]
Days to Secondary Endpoint
Mean (SD) 154 (78.2)
Median [Min, Max] 191 [21.0, 267]
Missing 3 (6.3%)
Endpoint 1: Ulcer Size (cm2)
Mean (SD) 0.925 (1.62)
Median [Min, Max] 0.200 [0, 8.10]
Endpoint 2: Ulcer Size (cm2)
Mean (SD) 1.17 (3.49)
Median [Min, Max] 0.100 [0, 22.7]
Missing 2 (4.2%)
Endpoint 1: Wound Healing Rate (cm2/week)
Mean (SD) 0.106 (0.252)
Median [Min, Max] 0.0600 [-0.190, 1.50]
Endpoint 2: Wound Healing Rate (cm2/week)
Mean (SD) 0.0864 (0.259)
Median [Min, Max] 0.0300 [-0.550, 1.50]
Missing 3 (6.3%)

Discrete Variables

Overall
(N=48)
Smoking History
Current 4 (8.3%)
Former 13 (27.1%)
Never 31 (64.6%)
History of Amputation
No 27 (56.3%)
Yes 20 (41.7%)
Missing 1 (2.1%)
Pet Owner
No 30 (62.5%)
Yes 13 (27.1%)
Missing 5 (10.4%)
Ulcer Site
1-2 submet 7 (14.6%)
5 submet 1 (2.1%)
digit 2 1 (2.1%)
hallux 12 (25.0%)
heel 4 (8.3%)
lateral 3 (6.3%)
medial 9 (18.8%)
sole 8 (16.7%)
sub 2-3 met 1 (2.1%)
Missing 2 (4.2%)
Healed at Primary Endpoint
No 31 (64.6%)
Yes 17 (35.4%)
Healed at Secondary Endpoint
No 22 (45.8%)
Yes 26 (54.2%)
Race
American Indian or Alaska Native 1 (2.1%)
Asian 1 (2.1%)
Black 8 (16.7%)
Native Hawaiian or other Pasific Islander 1 (2.1%)
Unknown 2 (4.2%)
White 35 (72.9%)
Reulceration During Study
No 43 (89.6%)
Yes 5 (10.4%)
Study Arm
Active 21 (43.8%)
Placebo 27 (56.3%)

Continuous and Discrete Variables Compared by Arm

  • Continuous variables compared by T-Test

  • Discrete variables compared by Fisher’s Test

Active
(N=21)
Placebo
(N=27)
P-value
Age
Mean (SD) 68.4 (7.49) 66.9 (7.85) 0.503
Median [Min, Max] 70.0 [56.0, 81.0] 67.0 [50.0, 83.0]
First HgbA1c
Mean (SD) 8.68 (1.20) 8.39 (1.48) 0.449
Median [Min, Max] 8.20 [6.70, 11.0] 8.20 [5.90, 11.8]
Monofilament Score
Mean (SD) 1.71 (3.16) 1.26 (1.99) 0.569
Median [Min, Max] 0 [0, 10.0] 0 [0, 7.00]
Duration of Diabetes
Mean (SD) 17.3 (8.68) 18.8 (10.5) 0.593
Median [Min, Max] 15.0 [5.00, 37.0] 21.0 [1.00, 51.0]
ABI
Mean (SD) 1.20 (0.186) 1.20 (0.254) 0.996
Median [Min, Max] 1.20 [0.920, 1.67] 1.16 [0.830, 2.04]
Missing 2 (9.5%) 6 (22.2%)
Smoking History
Current 1 (4.8%) 3 (11.1%) 0.385
Former 4 (19.0%) 9 (33.3%)
Never 16 (76.2%) 15 (55.6%)
History of Amputation
No 12 (57.1%) 15 (55.6%) 1
Yes 9 (42.9%) 11 (40.7%)
Missing 0 (0%) 1 (3.7%)
Pet Owner
No 12 (57.1%) 18 (66.7%)
Yes 6 (28.6%) 7 (25.9%)
Missing 3 (14.3%) 2 (7.4%)
Race
Asian 1 (4.8%) 0 (0%) 0.706
Black 4 (19.0%) 4 (14.8%)
White 16 (76.2%) 19 (70.4%)
American Indian or Alaska Native 0 (0%) 1 (3.7%)
Native Hawaiian or other Pasific Islander 0 (0%) 1 (3.7%)
Unknown 0 (0%) 2 (7.4%)
Charlson Comorbidity Index
Mean (SD) 2.76 (0.944) 2.59 (1.01) 0.553
Median [Min, Max] 2.00 [2.00, 4.00] 2.00 [2.00, 6.00]
DFU Severity Score
Mean (SD) 4.10 (1.87) 4.52 (2.19) 0.474
Median [Min, Max] 3.00 [3.00, 9.00] 4.00 [3.00, 11.0]
Initial Ulcer Age (weeks)
Mean (SD) 16.3 (18.2) 30.0 (38.2) 0.109
Median [Min, Max] 10.0 [3.00, 74.5] 12.0 [4.00, 165]
Initial Ulcer Size (cm2)
Mean (SD) 1.71 (2.34) 1.63 (1.41) 0.885
Median [Min, Max] 0.800 [0.300, 9.70] 1.20 [0.300, 5.50]
Ulcer Site
1-2 submet 4 (19.0%) 3 (11.1%)
hallux 5 (23.8%) 7 (25.9%)
heel 2 (9.5%) 2 (7.4%)
lateral 2 (9.5%) 1 (3.7%)
medial 4 (19.0%) 5 (18.5%)
sole 3 (14.3%) 5 (18.5%)
5 submet 0 (0%) 1 (3.7%)
digit 2 0 (0%) 1 (3.7%)
sub 2-3 met 0 (0%) 1 (3.7%)
Missing 1 (4.8%) 1 (3.7%)
Days to Primary Endpoint
Mean (SD) 74.4 (30.1) 85.3 (23.4) 0.178
Median [Min, Max] 91.0 [21.0, 112] 91.0 [40.0, 135]
Days to Secondary Endpoint
Mean (SD) 141 (75.5) 165 (80.2) 0.306
Median [Min, Max] 179 [21.0, 223] 210 [40.0, 267]
Missing 1 (4.8%) 2 (7.4%)
Endpoint 1: Ulcer Size (cm2)
Mean (SD) 0.681 (1.77) 1.11 (1.51) 0.374
Median [Min, Max] 0.100 [0, 8.10] 0.300 [0, 4.40]
Endpoint 2: Ulcer Size (cm2)
Mean (SD) 0.463 (0.894) 1.72 (4.54) 0.181
Median [Min, Max] 0 [0, 3.75] 0.300 [0, 22.7]
Missing 1 (4.8%) 1 (3.7%)
Endpoint 1: Wound Healing Rate (cm2/week)
Mean (SD) 0.174 (0.352) 0.0526 (0.115) 0.141
Median [Min, Max] 0.0600 [-0.140, 1.50] 0.0600 [-0.190, 0.430]
Endpoint 2: Wound Healing Rate (cm2/week)
Mean (SD) 0.154 (0.342) 0.0324 (0.153) 0.153
Median [Min, Max] 0.0600 [-0.0200, 1.50] 0.0300 [-0.550, 0.430]
Missing 1 (4.8%) 2 (7.4%)
Healed at Primary Endpoint
No 13 (61.9%) 18 (66.7%) 0.769
Yes 8 (38.1%) 9 (33.3%)
Healed at Secondary Endpoint
No 7 (33.3%) 15 (55.6%) 0.153
Yes 14 (66.7%) 12 (44.4%)
Reulceration During Study
No 18 (85.7%) 25 (92.6%) 0.641
Yes 3 (14.3%) 2 (7.4%)