Complementary Analysis

Complementary analysis:

Multiple imputation

In multiple imputation, missing values for any variable are predicted using existing values from other variables. Multiple imputation has been conducted to replace missing data for the following variables: index of lequesne, VAS for pain, paracetamol consumption, treatment efficacy and treatment safety. Our explicative variables were age, sex, bmi, number of paracetamol capsules intake and when it was possible, the preceeding variables of the same type (for example pain at D0 for Imputation of pain at D30).

Table 1 : General clinical examination and algo-functional Lequesne’s index

Sex of patient according to the treatment (imputation multiple)

Sex of patient according to the treatment / groupe / Ensemble
CHONDROSULF® 1200mg oral gel in sachet group / CHONDROSULF® 3x400mg capsules group / Control Group, Placebo
N / % / N / % / N / % / N / %
Male / 40 / 34.2 / 47 / 39.5 / 38 / 32.5 / 125 / 35.4
Female / 77 / 65.8 / 72 / 60.5 / 79 / 67.5 / 228 / 64.6
Total / 117 / 100.0 / 119 / 100.0 / 117 / 100.0 / 353 / 100.0

Khi² : 1.3845 p-value : 0.5004 Signification : NS

Age of patient according to the treatment (imputation multiple)

Age
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 65.4 / 10.4 / 66.0 / 28.0 / 88.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 65.3 / 8.8 / 66.0 / 48.0 / 85.0
Control Group, Placebo / 117 / 0 / 64.9 / 10.6 / 67.0 / 43.0 / 83.0
Total / 353 / 0 / 65.2 / 9.9 / 66.0 / 28.0 / 88.0

Anova : 0.0702 p-value : 0.9322 Signification : NS

BMI of patient according to the treatment (imputation multiple)

bmi_d0
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 28.9 / 5.2 / 28.4 / 17.7 / 44.2
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 28.4 / 4.4 / 27.5 / 20.2 / 47.5
Control Group, Placebo / 117 / 0 / 28.6 / 6.1 / 27.4 / 17.7 / 56.5
Total / 353 / 0 / 28.6 / 5.3 / 27.8 / 17.7 / 56.5

Anova : 0.3059 p-value : 0.7367 Signification : NS

Total score of algo functional index of lequesne according to the treatment (imputation multiple)

tleq_d0
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 11.9 / 3.1 / 11.5 / 7.0 / 20.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 11.2 / 2.6 / 11.0 / 7.0 / 18.5
Control Group, Placebo / 117 / 0 / 11.2 / 3.2 / 10.5 / 6.0 / 24.0
Total / 353 / 0 / 11.4 / 3.0 / 11.0 / 6.0 / 24.0

Anova : 2.0271 p-value : 0.1333 Signification : NS

Visual analogic scale for pain for the right knee according to the treatment
vask_d0
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 65.2 / 13.7 / 63.0 / 42.0 / 100.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 62.7 / 14.8 / 60.0 / 37.0 / 100.0
Control Group, Placebo / 117 / 0 / 62.5 / 15.0 / 61.0 / 25.0 / 100.0
Total / 353 / 0 / 63.5 / 14.5 / 62.0 / 25.0 / 100.0

Anova : 1.2452 p-value : 0.2892 Signification : NS

Table 2 : Equivalence for the change in the total score of algo-functional index of Lequesne between M0 and M3

(ITT LOCF)

Comparison between the 3 groups 2 by 2 / Equivalence at D91 for the total score of
algo functional index of lequesne according to the treatment
Delta / T-test confidence interval (95%) / Equivalence limit
Group 1200mg-Group3x400mg
((main criteria) / 0.33 / [-0.75; 1.41] / [-1; 1]
Group 1200mg-Placebo / 2.54 / [1.46; 3.63] / [-1; 1]
Group 3x400mg-Placebo / 2.21 / [1.13; 3.29] / [-1; 1]

(ITT imputation multiple)

Comparison between the 3 groups 2 by 2 / Equivalence at D91 for the total score of
algo functional index of lequesne according to the treatment
Delta / T-test confidence interval (95%) / Equivalence limit
Group 1200mg-Group3x400mg
((main criteria) / 0.25 / [-0.66; 1.16] / [-1; 1]
Group 1200mg-Placebo / 2.27 / [1.40; 3.15] / [-1; 1]
Group 3x400mg-Placebo / 2.03 / [1.15; 2.90] / [-1; 1]

(PP imputation multiple)

Comparison between the 3 groups 2 by 2 / Equivalence at D91 for the total score of
algo functional index of lequesne according to the treatment
Delta / T-test confidence interval (95%) / Equivalence limit
Group 1200mg-Group3x400mg
((main criteria) / 0.29 / [-0.67; 1.25] / [-1; 1]
Group 1200mg-Placebo / 2.52 / [1.63; 3.42] / [-1; 1]
Group 3x400mg-Placebo / 2.23 / [1.31; 3.16] / [-1; 1]

Table 3 : Change in Lequesne’s Index during the treatment period

Total score of algo functional index of lequesne according to the treatment (imputation multiple)

tleq_d0
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 11.9 / 3.1 / 11.5 / 7.0 / 20.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 11.2 / 2.6 / 11.0 / 7.0 / 18.5
Control Group, Placebo / 117 / 0 / 11.2 / 3.2 / 10.5 / 6.0 / 24.0
Total / 353 / 0 / 11.4 / 3.0 / 11.0 / 6.0 / 24.0

Anova : 2.0271 p-value : 0.1333 Signification : NS

tleq_d30
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 9.7 / 3.7 / 8.5 / 2.0 / 19.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 9.3 / 3.2 / 9.0 / 3.5 / 18.5
Control Group, Placebo / 117 / 0 / 10.0 / 3.7 / 9.5 / 1.0 / 22.5
Total / 353 / 0 / 9.7 / 3.5 / 9.0 / 1.0 / 22.5

Anova : 1.2820 p-value : 0.2788 Signification : NS

Scheffé : 1>3

tleq_d60
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 8.1 / 3.5 / 7.5 / 1.0 / 19.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 8.1 / 3.6 / 7.5 / 1.5 / 19.0
Control Group, Placebo / 117 / 0 / 9.6 / 4.1 / 9.5 / 0.0 / 21.0
Total / 353 / 0 / 8.6 / 3.8 / 8.5 / 0.0 / 21.0

Anova : 6.0306 p-value : 0.0027 Signification : <0.01

Scheffé : 1,2 >3

tleq_d91
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 7.6 / 4.0 / 6.5 / 0.5 / 18.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 7.1 / 3.9 / 7.0 / 0.0 / 17.5
Control Group, Placebo / 117 / 0 / 9.2 / 4.4 / 9.0 / 0.0 / 23.0
Total / 353 / 0 / 8.0 / 4.2 / 7.5 / 0.0 / 23.0

Anova : 8.3186 p-value : 0.0003 Signification : <0.001

Scheffé : 1,2 >3

Table 4 : Change in the global spontaneous pain during the treatment period

Visual analogic scale for pain according to the treatment

d0
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 65.2 / 13.7 / 63.0 / 42.0 / 100.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 62.7 / 14.8 / 60.0 / 37.0 / 100.0
Control Group, Placebo / 117 / 0 / 62.5 / 15.0 / 61.0 / 25.0 / 100.0
Total / 353 / 0 / 63.5 / 14.5 / 62.0 / 25.0 / 100.0

Anova : 1.2452 p-value : 0.2892 Signification : NS

d30
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 51.8 / 21.4 / 51.0 / 0.0 / 100.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 48.0 / 21.3 / 49.0 / 0.0 / 100.0
Control Group, Placebo / 117 / 0 / 49.9 / 21.4 / 51.0 / 3.0 / 100.0
Total / 353 / 0 / 49.9 / 21.4 / 50.0 / 0.0 / 100.0

Anova : 0.7499 p-value : 0.4732 Signification : NS

d60
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 40.9 / 22.3 / 38.0 / 0.0 / 100.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 41.0 / 23.6 / 41.0 / 0.0 / 97.0
Control Group, Placebo / 117 / 0 / 45.4 / 23.5 / 48.0 / 0.0 / 100.0
Total / 353 / 0 / 42.4 / 23.2 / 42.0 / 0.0 / 100.0

Anova : 1.4840 p-value : 0.2282 Signification : NS

d91
N / DM / Moyenne / Écart type / Médiane / Minimum / Maximum
CHONDROSULF® 1200mg oral gel in sachet group / 117 / 0 / 37.7 / 23.6 / 35.0 / 0.0 / 96.0
CHONDROSULF® 3x400mg capsules group / 119 / 0 / 36.5 / 25.4 / 30.0 / 0.0 / 100.0
Control Group, Placebo / 117 / 0 / 45.4 / 25.2 / 46.0 / 0.0 / 100.0
Total / 353 / 0 / 39.9 / 25.0 / 39.0 / 0.0 / 100.0

Anova : 4.5154 p-value : 0.0116 Signification : <0.05

Scheffé : 1,2 >3