Table 3.
Secondary outcomes at 96 weeks
| Amiloride (n=102) | Fluoxetine (n=97) | Riluzole (n=96) | Placebo (n=98) |
Amiloride vs placebo |
Fluoxetine vs placebo |
Riluzole vs placebo |
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|---|---|---|---|---|---|---|---|---|---|---|---|
| Adjusted mean difference (95% CI)* | p value | Adjusted mean difference (95% CI)* | p value | Adjusted mean difference (95% CI)* | p value | ||||||
| Expanded Disability Status Scale score† | 6·0 (1·0) | 5·9 (1·2) | 6·0 (1·1) | 6·0 (1·1) | 0·1 (−0·1 to 0·2) | 0·61 | −0·1 (−0·3 to 0·2) | 0·54 | 0·1 (−0·2 to 0·2) | 0·63 | |
| Multiple Sclerosis Functional Composite score (Z-score)‡ | −0·55 (1·87) | −0·53 (1·66) | −0·47 (1·69) | −0·41 (1·78) | 0·06 (−0·15 to 0·27) | 0·59 | −0·09 (−0·30 to 0·12) | 0·42 | 0·02 (−0·19 to 0·23) | 0·84 | |
| Paced Auditory Serial Addition Test | 41·1 (14·3) | 36·8 (16·3) | 38·4 (15·6) | 41·9 (16·7) | 0·9 (−1·9 to 3·7) | 0·51 | −1·1 (−3·9 to 1·8) | 0·47 | 0·4 (−2·4 to 3·3) | 0·76 | |
| 9-Hole Peg Test (s−1) | 0·03 (0·01) | 0·03 (0·01) | 0·03 (0·01) | 0·03 (0·01) | 0·00 (−0·00 to 0·00) | 0·36 | 0·00 (−0·00 to 0·00) | 0·85 | 0·00 (−0·00 to 0·00) | 0·27 | |
| Symbol Digit Modalities Test | 43·0 (14·9) | 44·8 (13·7) | 44·9 (14·2) | 46·1 (14·5) | −1·0 (−3·1 to 1·0) | 0·32 | −1·1 (−3·2 to 0·9) | 0·29 | −0·8 (−2·9 to 1·3) | 0·44 | |
| High contrast (100%) visual acuity | 50·1 (10·9) | 50·5 (11·2) | 47·8 (15·8) | 49·1 (13·7) | 3·0 (0·5 to 5·6) | 0·020 | 1·8 (−0·7 to 4·4) | 0·16 | 1·6 (−1·0 to 4·2) | 0·22 | |
| Sloan low contrast visual acuity | |||||||||||
| 5% contrast | 31·8 (12·9) | 32·6 (13·1) | 31·2 (15·6) | 32·4 (13·5) | 1·0 (−1·8 to 3·8) | 0·49 | 1·3 (−1·6 to 4·1) | 0·38 | 1·5 (−1·4 to 4·3) | 0·32 | |
| 2·5% contrast | 17·1 (14·2) | 16·5 (13·2) | 17·7 (14·2) | 18·1 (13·4) | 0·9 (−2·0 to 3·7) | 0·55 | 1·3 (−1·5 to 4·1) | 0·37 | 1·7 (−1·2 to 4·6) | 0·25 | |
| 1·25% contrast | 5·2 (8·8) | 4·0 (8·2) | 6·1 (10·4) | 6·8 (9·7) | −0·6 (−2·7 to 1·5) | 0·58 | −0·8 (−2·9 to 1·3) | 0·46 | 0·7 (−1·4 to 2·9) | 0·49 | |
| Multiple Sclerosis Impact Scale 29 items version 2 | |||||||||||
| Total score | 72·3 (16·3) | 69·7 (15·1) | 72·9 (15·8) | 69·5 (17·2) | 3·7 (0·2 to 7·2) | 0·037 | 0·5 (−3·0 to 4·0) | 0·79 | 0·9 (−2·6 to 4·5) | 0·60 | |
| Physical score | 53·2 (12·0) | 52·1 (11·4) | 53·6 (12·4) | 51·3 (12·7) | 2·2 (−0·3 to 4·7) | 0·089 | 0·7 (−1·8 to 3·3) | 0·57 | 0·6 (−2·0 to 3·1) | 0·66 | |
| Psychological score | 19·1 (6·1) | 17·7 (5·3) | 19·3 (5·4) | 18·3 (5·8) | 1·5 (0·2 to 2·8) | 0·025 | −0·3 (−1·6 to 1·0) | 0·68 | 0·5 (−0·9 to 1·8) | 0·49 | |
| Multiple Sclerosis Walking Scale version 2 | 44·2 (9·4) | 44·4 (8·8) | 44·6 (9·6) | 43·6 (10·1) | 0·5 (−1·6 to 2·5) | 0·66 | 1·0 (−1·1 to 3·1) | 0·35 | 0·6 (−1·5 to 2·8) | 0·55 | |
| Neurological Fatigue Index | |||||||||||
| Summary score | 19·4 (5·3) | 18·3 (4·0) | 19·7 (4·8) | 18·3 (5·5) | 0·9 (−0·2 to 2·0) | 0·11 | 0·5 (−0·6 to 1·7) | 0·36 | 0·7 (−0·4 to 1·9) | 0·20 | |
| Physical score | 16·3 (4·5) | 15·4 (3·8) | 16·4 (4·2) | 15·0 (4·8) | 1·2 (0·2 to 2·3) | 0·019 | 0·7 (−0·3 to 1·8) | 0·17 | 1·0 (−0·0 to 2·1) | 0·061 | |
| Cognitive score | 7·1 (2·5) | 6·7 (2·1) | 7·4 (2·1) | 6·8 (2·9) | 0·1 (−0·4 to 0·6) | 0·70 | 0·2 (−0·4 to 0·7) | 0·55 | 0·2 (−0·4 to 0·7) | 0·55 | |
| Diurnal score | 10·7 (3·2) | 10·3 (2·9) | 10·7 (2·5) | 10·6 (2·6) | −0·3 (−0·9 to 0·3) | 0·36 | −0·3 (−1·0 to 0·3) | 0·29 | −0·3 (−0·9 to 0·4) | 0·40 | |
| Nocturnal score | 8·7 (2·1) | 8·3 (2·3) | 8·4 (2·5) | 8·2 (2·2) | 0·6 (0·1 to 1·1) | 0·013 | 0·4 (−0·1 to 0·9) | 0·12 | 0·1 (−0·4 to 0·6) | 0·65 | |
| EQ-5D-5L | |||||||||||
| Index score | 0·60 (0·23) | 0·62 (0·21) | 0·60 (0·19) | 0·61 (0·22) | −0·01 (−0·06 to 0·04) | 0·69 | −0·02 (−0·06 to 0·03) | 0·52 | −0·01 (−0·05 to 0·04) | 0·82 | |
| VAS score | 66·1 (16·9) | 67·5 (19·5) | 61·7 (21·0) | 65·2 (20·3) | −2·1 (−7·6 to 3·5) | 0·47 | −3·0 (−8·6 to 2·6) | 0·29 | −3·0 (−8·6 to 2·7) | 0·30 | |
| New or enlarging T2 lesions | 3·7 (8·1) | 1·8 (5·3) | 2·8 (5·7) | 3·0 (6·9) | 1·2 (0·8 to 1·8) | 0·29 | 0·5 (0·3 to 0·9) | 0·012 | 1·0 (0·6 to 1·5) | 0·81 | |
Data are mean (SD). Results are derived from a model analysing data for 393 participants who had at least some 96-week outcome data. Numbers of patients are the maximum per group; the minimum sample size was n=380 for each secondary outcome (minimum per group: amiloride, n=98; fluoxetine, n=94; riluzole, n=92; placebo, n=94). The multiple regression model for each outcome included randomised treatment as an explanatory factor variable (with placebo as the reference category), the baseline measurement, and minimisation variables (age, sex, treatment centre, and Expanded Disability Status Scale score at baseline). EQ-5D-5L=EuroQol five dimensions five levels. VAS=visual analogue scale.
Effect sizes are adjusted mean difference (95% CI), except for new or enlarging T2 lesions, which is the adjusted rate ratio (investigational drug:placebo) and 95% CI.
95% CIs calculated using 1000 bootstrap resamples.
The Multiple Sclerosis Functional Composite score was signed square-root transformed before analysis.