Table 3.
Results for secondary outcome measures by aerobic physical fitness training or relaxation sessions (control group)
| Secondary outcomes by groups | Baseline: aerobic physical fitness training (n=105), relaxation sessions (n=95) | Post-intervention: aerobic physical fitness training (n=87), relaxation sessions (n=85) | Follow-up | Treatment effect (95%CI)* | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 3 months: aerobic physical fitness training (n=89), relaxation sessions (n=77) | 6 months: aerobic physical fitness training (n=79), relaxation sessions (n=65) | Post-intervention | 3 months follow-up | 6 months follow-up | ||||||
| Median (interquartile range); mean (SD) maximal walking speed (m/s)† | ||||||||||
| Aerobic training | 0.2 (0.1-0.5); 0.4 (0.4) | 0.4 (0.2-0.8); 0.6 (0.5) | 0.6 (0.3-1.1); 0.8 (0.6) | 0.8 (0.3-1.3); 0.9 (0.8) | 0.03 (−0.10 to 0.16) | Primary outcome | 0.09 (−0.04 to 0.22) | |||
| Relaxation | 0.3 (0.1-0.7); 0.5 (0.4) | 0.6 (0.3-0.8); 0.6 (0.6) | 0.6 (0.4-0.9); 0.8 (0.7) | 0.8 (0.4-1.3); 0.9 (0.9) | ||||||
| Median (interquartile range); mean (SD) Barthel index score | ||||||||||
| Aerobic training | 50 (35-60); 47 (16) | 75 (60-90) 73 (21) | 80 (61-100); 77 (22) | 90 (70-100); 82 (20) | 0 (−4 to 5) | Primary outcome | −1 (−6 to 3) | |||
| Relaxation | 55 (35-65); 49 (17) | 80 (60-90); 75 (22) | 80 (70-95); 79 (19) | 90 (70-100); 84 (18) | ||||||
| Median (interquartile range); mean (SD) 6 minute walk distance (m)‡ | ||||||||||
| Aerobic training | 75 (32-160); 107 (110) | 145 (85-245); 175 (126) (n=81) | 165 (90-300); 201 (153) (n=85) | 220 (110-350); 239 (152) (n=77) | 19 (−8 to 46) | 27 (0 to 54) | 26 (−1 to 53) | |||
| Relaxation | 120 (39-205); 139 (113) | 179 (91-244); 185 (115) (n=78) | 180 (110-263); 203 (128) (n=71) | 208; (114-323) 233 (149) (n=64) | ||||||
| Mean (SD) Rivermead mobility index score | ||||||||||
| Aerobic training | 5 (3) | 8 (4) | 9 (4) | 11 (4) | 0.2 (−0.6 to 1.0) | 0.3 (−0.5 to 1.1) | 0.0 (−0.8 to 0.8) | |||
| Relaxation | 6 (3) | 9 (4) | 9 (4) | 11 (4) (n=65) | ||||||
| Median (interquartile range) modified Ranking scale score | ||||||||||
| Aerobic training | 4 (4-4) | 4 (3-4) | 3 (2-4) (n=90) | 3 (2-4) | 2.0 (0.6 to 6.9)§ | 0.8 (0.2 to 2.5)§ | 1.1 (0.3 to 3.6)§ | |||
| Relaxation | 4 (3-4) | 3 (3-4) | 3 (3-4) (n=78) | 3 (2-4) | ||||||
| Median (interquartile range) actigraphy (steps/day)¶ | ||||||||||
| Aerobic training | 3263 (1815-5515); (n=97) | 4758 (2910-7056); (n=70) | 4215 (2042-6399); (n=77) | 4284 (2193-7308); (n=63) | −555 (−1486 to 375) | −539 (−1467 to 394) | −566 (−1497 to 365) | |||
| Relaxation | 3503 (1949-6328); (n=88) | 5183 (2945-7876); (n=75) | 5160 (3194-7980); (n=69) | 6105 (3404-7904); (n=53) | ||||||
| Median (interquartile range) step length (m)** | ||||||||||
| Aerobic training | 0.31 (0.23-0.44); (n=99) | 0.39 (0.30-0.51); (n=85) | 0.43 (0.29-0.56); (n=88) | 0.50 (0.35-0.63); (n=78) | 0.04 (−0.01 to 0.07) | 0.03 (−0.02 to 0.07) | 0.03 (−0.01 to 0.07) | |||
| Relaxation | 0.39 (0.29-0.48); (n=93) | 0.40 (0.30-0.50); (n=83) | 0.42 (0.34-0.56); (n=76) | 0.47 (0.33-0.64); (n=64) | ||||||
| No (%) used walking aid | ||||||||||
| Aerobic training | 69 (75) (n=92) | 57 (71) (n=80) | 55 (63) (n=88) | 48 (60) (n=79) | 0.46§ (0.10 to 2.19) | 0.29§ (0.06 to 1.41) | 0.30§ (0.06 to 1.57) | |||
| Relaxation | 60 (78) (n=77) | 59 (76) (n=78) | 52 (72) (n=72) | 42 (68) (n=62) | ||||||
| Median (interquartile range) step cadence (steps/min)†† | ||||||||||
| Aerobic training | 53 (29-91); (n=99) | 68 (46-102); (n=84) | 91 (54-116); (n=88) | 100 (59-128); (n=78) | 2 (−7 to 12) | 6 (−4 to 15) | 3 (−7 to 12) | |||
| Relaxation | 70 (36-92); (n=93) | 80 (57-99); (n=83) | 90 (65-113); (n=76) | 98 (68-126); (n=64) | ||||||
| Median (interquartile range) box and block test, impaired hand/non-impaired hand‡‡ | ||||||||||
| Aerobic training | 0 (0-31) / 46 (34-54) (n=100) | 12 (0-38) / 48 (40-58) / | 19 (0-39) / 53 (40-62) | 27 (0-44) / 54 (42-62) | 1 (−3 to 6) | 1 (−3 to 5) | −1 (−6 to 3) | |||
| Relaxation | 2 (0-23) / 45 (35-52) (n=89) | 12 (0-34) / 46 (39-56) / | 23 (0-35) / 45 (38-56) | 28 (3-43) / 50 (39-60) | ||||||
| Mean (SD) Rivermead mobility index score: subtest arm | ||||||||||
| Aerobic training | 5 (5) | 6 (6) | 6 (6) | 8 (6) | −0.7 (−1.6 to 0.2) | −0.9 (−1.8 to 0.0) | −1.1 (−2.0 to 0.0) | |||
| Relaxation | 5 (5) | 7 (5) | 8 (5) | 9 (5) | ||||||
| Mean (SD) medical research council scale, sum score over six items§§ | ||||||||||
| Aerobic training | 19 (8) (n=104) | 22 (7) (n=86) | 22 (6) | 23 (7) | 0.3 (−0.8 to 1.4) | −0.3 (−1.4 to 0.8) | −0.2 (−1.3 to 0.9) | |||
| Relaxation | 20 (8) | 22 (7) (n=85) | 23 (7) | 24 (5) | ||||||
| Mean (SD) resistance to passive movement scale sum score | ||||||||||
| Aerobic training | 4 (5) | 6 (6) | 8 (9) (n=88) | 11 (14) | 0.9 (−1.0 to 2.9) | 1.6 (−0.3 to 3.6) | 2.6 (0.6 to 4.5) | |||
| Relaxation | 4 (5) | 5 (6) | 6 (7) (n=77) | 9 (9) | ||||||
| Median (interquartile range ) functional ambulation category score¶¶ | ||||||||||
| Aerobic training | 2 (1-2) | 3 (2-3) (n=56) | 3 (2-4) (n=52) | 4 (2-5) (n=47) | 0.3 (0.1 to 1.6)§ | 0.9 (0.2 to 5.0)§ | 1.1 (0.2 to 6.2)§ | |||
| Relaxation | 2 (1-3) | 3 (2-4) (n=57) | 3 (2-4) (n=44) | 3 (3-4) (n=33) | ||||||
| Median (interquartile range) gait energy cost (ml/kg-1/m-1)*** | ||||||||||
| Aerobic training | 0.8 (0.4-1.2) (n=54) | 0.4 (0.3-0.6) (n=51) | 0.4 (0.3-0.6) (n=49) | 0.3 (0.2-0.5) (n=35) | −0.1 (−0.2 to 0.0) | −0.1 (−0.2 to 0.0) | −0.1 (−0.2 to 0.0) | |||
| Relaxation | 0.4 (0.3-0.7) (n=46) | 0.4 (0.3-0.5) (n=41) | 0.4 (0.3-0.6) (n=41) | 0.4 (0.3-0.5) (n=32) | ||||||
| Mean (SD) quality of life (EQ-5D-5L) index score††† | ||||||||||
| Aerobic training | 0.5 (0.3) (n=104) | 0.7 (0.3) (n=87) | 0.7 (0.3) (n=87) | 0.7 (0.3) | 0.04 (−0.04 to 0.11) | 0.03 (−0.05 to 0.11) | 0.0 (−0.08 to 0.08) | |||
| Relaxation | 0.5 (0.3) (n=93) | 0.7 (0.3) (n=82) | 0.6 (0.3) (n=77) | 0.7 (0.3) | ||||||
| Mean (SD) depression (CES-D) sum score‡‡‡ | ||||||||||
| Aerobic training | 10 (7) (n=85) | 9 (6) (n=72) | 10 (7) (n=71) | 8 (7) | −1 (−3 to 1) | 0 (−2 to 2) | 0 (−2 to 1) | |||
| Relaxation | 10 (5) (n=72) | 10 (5) (n=67) | 10 (6) (n=64) | 9 (5) | ||||||
| Mean (SD) sleep (PSQI) sum score§§§ | ||||||||||
| Aerobic training | 4 (3) (n=96) | 5 (4) (n=83) | 6 (3) (n=84) | 5 (4) (n=77) | −1 (−2 to 0) | −1 (−1 to 0) | −1 (−1 to 0) | |||
| Relaxation | 5 (3) (n=88) | 6 (4) (n=78) | 6 (4) (n=74) | 5 (3) (n=60) | ||||||
| Median (interquartile range) cognition (MOCA) sum score¶¶¶ | ||||||||||
| Aerobic training | 24 (21-27) (n=104) | 26 (22-28) (n=86) | 25 (22-28) (n=89) | 26 (24-29) | 0 (−1 to 1) | −1 (−1 to 1) | 0 (−1 to 1) | |||
| Relaxation | 24 (17-26) (n=94) | 25 (19-27) (n=84) | 25 (21-28) (n=75) | 26 (21-28) (n=64) | ||||||
| Median (interquartile range) cognitive processing speed (TMT A) (sec)**** | ||||||||||
| Aerobic training | 70 (52-122) (n=104) | 56 (42-120) (n=85) | 51 (37-84) | 52 (33-69) | 5 (−10 to 20) | 7 (−7 to 22) | 1 (−14 to 16) | |||
| Relaxation | 85 (60-197) (n=94) | 64 (47-123) (n=84) | 67 (43-102) | 60 (42-82) | ||||||
| Median (interquartile range) executive functioning (TMT B) (sec)†††† | ||||||||||
| Aerobic training | 222 (127-301) (n=104) | 97 (93-301) (n=85) | 139 (88-301) | 125 (78-216) | −5 (−21 to 11) | −1 (−17 to 16) | −6 (−22 to 10) | |||
| Relaxation | 301 (157-301) (n=93) | 218 (134-301) (n=84) | 166 (110-301) | 150 (92-301) | ||||||
| Mean (SD) word fluency (RWT) sum score‡‡‡‡ | ||||||||||
| Aerobic training | 38 (19) (n=104) | - | 43 (19) (n=86) | - | - | 1 (−2 to 3) | - | |||
| Relaxation | 34 (18) (n=92) | - | 40 (18) (n=73) | - | ||||||
Analyses are based on mixed models analysis of covariance (adjusted for baseline value, age, sex, functional ambulation category, and centre heterogeneity). Estimates are based on three level mixed models and multiple imputation (n=600 measures, 200 participants, six study centres) positive values favour aerobic physical fitness training. Missing values were imputed by multiple imputation, except for modified Ranking scale score, use of walking aids, and functional ambulation category (imputation process was done separately for treatment groups). If the number of valid data points differs for specific variables, the number of available data points is listed in brackets. Data missing due to missing at random are imputed (see supplementary appendix).
Secondary outcomes are exploratory and not meant for hypothesis testing. P values are therefore not reported.
21 participants were unable to walk 10 m to assess maximal walking speed—values were therefore imputed using single value imputation by taking half of lowest value of total cohort.
17 participants were unable to walk for entire time of six minutes—for those participants distance walked up to stopping is used. 28 participants were in poor physical condition and could not do the test—values were therefore imputed, using single value imputation by taking half of lowest value of total cohort.
Difference between groups at three months after stroke presented as odds ratios (95% confidence intervals, odds ratio >1 favours aerobic training intervention. Calculations not adjusted for centre heterogeneity. For walking aids odds ratio >1 means dependence on walking aids in aerobic training group. Table 2 shows results for primary efficacy outcomes.
15 baseline actigraphy values were missing due to logistic reasons. Data are assumed to be missing completely at random.
Missing values in step length are due to implausible number of steps within 10 m gait assessment, or 10 m walk test not completed.
Missing values in step cadence are due to implausible number of steps within 10 m gait assessment, or 10 m walk test not completed.
11 participants showed no initial motor impairment and are excluded from analysis.
One baseline value on medical research council scale is missing at random in aerobic group.
Functional ambulation category was initially assessed at baseline only and not at follow-up; therefore some follow-up values are missing.
Spirometry data are missing mostly due to technical issues. Baseline values are available for 100 participants (n=54 aerobic training, n=46 relaxation).
Six baseline values for EuroQol quality of life questionnaire (EQ-5D-5L) index score were missing for various reasons (aphasia, fatigue, understanding difficulties).
19 baseline values for Center for Epidemiologic Studies depression scale (CES-D) sum score were missing owing to aphasia, fatigue, understanding difficulties, not able to respond to question. 24 data points had to be excluded because participants fulfilled criteria for unreliable data (lie, criteria ≤28).
16 baseline values for Pittsburgh sleep quality index (PSQI) sum score were missing owing to aphasia, fatigue, and understanding difficulties.
Two baseline values for Montreal cognitive assessment (MOCA) sum score were missing owing to fatigue.
Two baseline values for trail making test (TMT) part A were missing owing to poor vision and fatigue.
Three baseline values for trail making test (TMT) part B were missing owing poor vision, fatigue, and failure of time recording by assessor.
The Regensburger Wortflüssigkeitstest (RWT) was only assessed at baseline and at three months’ follow-up. Four baseline values for RWT were missing owing to severe aphasia.