Background
Methods
Overview of the design of the trial
Inclusion and exclusion criteria
Randomization
Treatment
Blood pressure measurement
Other measurements
Statistical analyses
Results
Subject characteristics
Characteristic | 0.05 mg/d | 0.15 mg/d | 0.5 mg/d | 1.5 mg/d | 5.0 mg/d | |||||
---|---|---|---|---|---|---|---|---|---|---|
P/R (N = 43) | R/P (N = 44) | P/R (N = 44) | R/P (N = 44) | P/R (N = 41) | R/P (N = 44) | P/R (N = 44) | R/P (N = 44) | P/R (N = 44) | R/P (N = 43) | |
Mean (± SD) of baseline characteristic | ||||||||||
Age, years | 48.1 ± 7.8 | 50.4 ± 7.4 | 46.8 ± 8.6 | 48.2 ± 8.0 | 48.8 ± 7.2 | 49.7 ± 7.5 | 49.0 ± 6.7 | 48.5 ± 8.5 | 49.7 ± 7.9 | 44.9 ± 8.4 |
BMI, kg/m2
| 27.1 ± 2.7 | 27.6 ± 2.3 | 26.4 ± 2.7 | 26.9 ± 2.2 | 26.3 ± 2.7 | 27.0 ± 2.5 | 25.9 ± 3.0 | 26.9 ± 2.4 | 25.8 ± 2.5 | 26.7 ± 2.7 |
Pulse rate, beats/min | 77.0 ± 10.8 | 77.6 ± 10.3 | 75.8 ± 12.8 | 74.4 ± 9.8 | 75.2 ± 11.0 | 76.8 ± 12.3 | 74.2 ± 11.8 | 80.5 ± 11.5 | 75.8 ± 13.0 | 77.3 ± 10.0 |
Systolic BP, mm Hg | ||||||||||
Office | 148.7 ± 7.3 | 150.9 ± 7.4 | 148.0 ± 5.8 | 150.5 ± 8.4 | 150.4 ± 7.6 | 152.5 ± 8.7 | 150.8 ± 7.6 | 151.1 ± 7.8 | 150.6 ± 6.7 | 149.4 ± 7.2 |
24-h ambulatory* | 136.8 ± 9.5 | 137.3 ± 11.3 | 135.3 ± 10.4 | 134.9 ± 10.9 | 140.9 ± 11.0 | 137.4 ± 9.6 | 138.1 ± 11.2 | 137.8 ± 11.8 | 138.6 ± 11.4 | 136.2 ± 11.7 |
Daytime* | 144.4 ± 9.9 | 143.7 ± 12.5 | 141.8 ± 10.4 | 142.3 ± 12.3 | 147.1 ± 12.7 | 142.9 ± 10.1 | 145.0 ± 13.6 | 144.5 ± 12.5 | 145.2 ± 12.6 | 142.2 ± 12.7 |
Night-time* | 122.2 ± 11.9 | 123.5 ± 13.8 | 122.5 ± 14.8 | 119.9 ± 11.3 | 126.4 ± 12.2 | 125.6 ± 12.6 | 125.7 ± 11.7 | 123.5 ± 14.7 | 125.5 ± 13.0 | 122.8 ± 15.4 |
Diastolic BP, mm Hg | ||||||||||
Office | 92.1 ± 7.6 | 93.0 ± 7.0 | 91.9 ± 7.2 | 92.4 ± 7.2 | 92.3 ± 6.9 | 95.9 ± 7.2 | 92.0 ± 7.9 | 94.2 ± 8.2 | 92.8 ± 6.4 | 93.9 ± 6.5 |
24-h ambulatory* | 85.5 ± 7.9 | 84.1 ± 7.2 | 84.5 ± 7.6 | 84.2 ± 8.4 | 88.1 ± 9.4 | 87.6 ± 8.8 | 86.5 ± 7.3 | 85.6 ± 8.4 | 86.9 ± 7.0 | 85.0 ± 9.0 |
Daytime* | 91.6 ± 8.2 | 89.7 ± 8.8 | 90.2 ± 7.5 | 90.2 ± 9.5 | 93.2 ± 10.9 | 92.3 ± 9.1 | 91.5 ± 8.8 | 91.0 ± 8.8 | 92.5 ± 8.3 | 89.6 ± 10.0 |
Night-time* | 73.4 ± 9.7 | 72.7 ± 8.4 | 74.3 ± 10.8 | 72.3 ± 7.8 | 77.1 ± 9.5 | 78.4 ± 10.8 | 77.1 ± 8.6 | 74.7 ± 11.0 | 76.6 ± 7.7 | 74.2 ± 10.5 |
Number (%) with baseline characteristic | ||||||||||
Women | 20 (46.5) | 18 (40.9) | 21 (47.7) | 15 (34.1) | 12 (29.3) | 14 (31.8) | 21 (47.7) | 16 (36.4) | 22 (50.0) | 18 (41.9) |
Caucasian | 43 (100) | 44 (100) | 44 (100) | 44 (100) | 41 (100) | 42 (95.5) | 43 (97.7) | 43 (97.7) | 44 (100) | 43 (100) |
Previous AH treatment | 14 (32.6) | 14 (31.8) | 22 (50.0) | 20 (45.5) | 18 (43.9) | 24 (54.5) | 23 (52.3) | 22 (50.0) | 18 (40.9) | 18 (41.9) |
Current smokers | 5 (11.6) | 7 (15.9) | 6 (13.6) | 9 (20.5) | 6 (14.6) | 8 (18.2) | 5 (11.4) | 7 (15.9) | 14 (31.8) | 12 (27.9) |
Current alcohol intake | 21 (48.8) | 23 (52.3) | 19 (43.2) | 23 (52.3) | 22 (53.7) | 21 (47.7) | 18 (40.9) | 23 (52.3) | 20 (45.5) | 27 (62.8) |
Blood pressure
Mean level ± SD at end of treatment period | Mean difference (95% CI) |
P-values | |||||
---|---|---|---|---|---|---|---|
N | Placebo | Rostafuroxin | Rostafuroxin minus placebo | Treatment effect | Carryover effect | Period effect | |
Systolic pressure, mm Hg | |||||||
0.05 mg | 83 | 142.0 ± 11.1 | 144.7 ± 12.2 | 2.72 (0.07 to 5.36) | 0.044 | 0.352 | 0.229 |
0.15 mg | 82 | 143.6 ± 13.5 | 143.3 ± 13.9 | -0.18(-3.21 to 2.85) | 0.905 | 0.897 | 0.364 |
0.5 mg | 77 | 145.3 ± 13.8 | 145.9 ± 13.3 | 0.49 (-2.38 to 3.36) | 0.732 | 0.326 | 0.770 |
1.5 mg | 86 | 145.8 ± 13.7 | 146.8 ± 15.1 | 1.11 (-1.32 to 3.54) | 0.366 | 0.828 | 0.723 |
5.0 mg | 82 | 142.1 ± 12.1 | 144.5 ± 14.3 | 2.29 (-0.35 to 4.93) | 0.089 | 0.667 | 0.038 |
All doses | 410 | 143.7 ± 12.9 | 145.1 ± 13.8 | 1.30 (0.10 to 2.50) | 0.034 | 0.963 | 0.028 |
Diastolic pressure, mm Hg | |||||||
0.05 mg | 83 | 88.1 ± 8.3 | 89.9 ± 9.2 | 1.76 (0.01 to 3.51) | 0.049 | 0.846 | 0.639 |
0.15 mg | 82 | 88.7 ± 9.1 | 88.5 ± 9.6 | -0.25 (-2.03 to 1.54) | 0.786 | 0.596 | 0.296 |
0.5 mg | 77 | 90.6 ± 8.8 | 90.6 ± 8.2 | 0.02 (-1.92 to 1.95) | 0.986 | 0.112 | 0.905 |
1.5 mg | 86 | 90.5 ± 9.5 | 91.5 ± 8.9 | 0.98 (-0.65 to 2.61) | 0.235 | 0.580 | 0.027 |
5.0 mg | 82 | 88.4 ± 8.1 | 89.4 ± 8.5 | 0.97 (-1.01 to 2.95) | 0.333 | 0.431 | 0.163 |
All doses | 410 | 89.3 ± 8.8 | 90.0 ± 8.9 | 0.70 (-0.09 to 1.50) | 0.084 | 0.364 | 0.018 |
Mean level ± SD at end of treatment period | Mean difference (95% CI) |
P-values | |||||
---|---|---|---|---|---|---|---|
N | Placebo | Rostafuroxin | Rostafuroxin minus placebo | Treatment effect | Carryover effect | Period effect | |
Systolic pressure, mm Hg | |||||||
0.05 mg | 79 | 133.1 ± 10.8 | 134.1 ± 11.2 | 0.99 (-1.42 to 3.40) | 0.417 | 0.398 | 0.324 |
0.15 mg | 76 | 134.8 ± 13.3 | 134.7 ± 12.0 | -0.07 (-2.73 to 2.58) | 0.957 | 0.348 | 0.166 |
0.5 mg | 72 | 137.0 ± 10.7 | 137.0 ± 10.8 | 0.08 (-2.27 to 2.43) | 0.945 | 0.790 | 0.889 |
1.5 mg | 80 | 136.7 ± 13.1 | 137.8 ± 10.7 | 1.11 (-1.04 to 3.26) | 0.306 | 0.753 | 0.741 |
5.0 mg | 76 | 136.3 ± 11.8 | 135.9 ± 12.9 | -0.36 (-2.37 to 1.64) | 0.719 | 0.854 | 0.696 |
All doses | 383 | 135.6 ± 12.0 | 135.9 ± 11.6 | -0.36 (-0.67 to 1.38) | 0.493 | 0.926 | 0.860 |
Diastolic pressure, mm Hg | |||||||
0.05 mg | 79 | 82.5 ± 8.3 | 83.2 ± 8.3 | 0.75 (-0.92 to 2.41) | 0.374 | 0.611 | 0.446 |
0.15 mg | 76 | 83.4 ± 9.0 | 83.1 ± 9.3 | -0.29(-2.03 to 1.45) | 0.743 | 0.467 | 0.155 |
0.5 mg | 72 | 86.2 ± 8.4 | 85.2 ± 9.0 | -1.01(-2.59 to 0.58) | 0.210 | 0.459 | 0.630 |
1.5 mg | 80 | 84.9 ± 9.3 | 85.4 ± 7.7 | 0.56 (-0.66 to 1.77) | 0.365 | 0.900 | 0.559 |
5.0 mg | 76 | 84.7 ± 8.5 | 84.8 ± 8.6 | 0.18 (-1.11 to 1.46) | 0.785 | 0.687 | 0.677 |
All doses | 383 | 84.3 ± 8.8 | 84.3 ± 8.6 | 0.05 (-0.61 to 0.72) | 0.882 | 0.457 | 0.971 |
Excretion of electrolytes
Mean level at the end of treatment period | Mean difference (95% CI) |
P-values | |||||
---|---|---|---|---|---|---|---|
N | Placebo | Rostafuroxin | Active minus placebo | Treatment effect | Carryover effect | Period effect | |
Sodium (μmol/min) | |||||||
Whole day | 386 | 122.3 ± 53.1 | 117.3 ± 50.4 | -5.1 (-10.5 to 0.4) | 0.071 | 0.546 | 0.256 |
Daytime | 386 | 128.2 ± 69.8 | 126.3 ± 86.7 | -1.9 (-10.9 to 7.0) | 0.672 | 0.802 | 0.880 |
Nighttime | 386 | 115.6 ± 87.4 | 107.6 ± 67.8 | -8.0 (-16.4 to 0.4) | 0.061 | 0.710 | 0.112 |
Potassium (μmol/min) | |||||||
Whole day | 386 | 43.7 ± 22.1 | 43.5 ± 20.2 | -0.2 (-2.6 to 2.2) | 0.844 | 0.942 | 0.685 |
Daytime | 386 | 49.5 ± 29.1 | 50.7 ± 38.4 | 1.2 (-2.8 to 5.2) | 0.545 | 0.641 | 0.320 |
Nighttime | 386 | 33.4 ± 27.3 | 32.3 ± 21.8 | -1.1 (-4.2 to 2.0) | 0.479 | 0.692 | 0.775 |
Sodium/potassium ratio | |||||||
Whole day | 386 | 2.84 (0.99 to 7.74) | 2.72 (0.96 to 8.13) | 0.96 (0.90 to 1.01) | 0.122 | 0.434 | 0.154 |
Daytime | 386 | 2.64 (0.81 to 8.29) | 2.53 (0.77 to 8.66) | 0.96 (0.90 to 1.02) | 0.196 | 0.490 | 0.273 |
Nighttime | 386 | 3.46 (1.03 to 10.6) | 3.34 (1.06 to 11.6) | 0.97 (0.90 to 1.04) | 0.327 | 0.093 | 0.314 |
Plasma ouabain (pmol/L) | 357 | 155.4 (56.8 to 453) | 161.6 (57.7 to 425.0) | 1.04 (0.98 to 1.10) | 0.192 | 0.997 | 0.369 |
Plasma renin activity (ng/mL/h) | 374 | 0.57 (0.11 to 2.62) | 0.57 (0.12 to 2.95) | 1.00 (0.94 to 1.07) | 0.948 | 0.087 | 0.672 |
Aldosterone excretion (nmol/24 h) | 334 | 25.7 (5.96 to 130) | 25.5(4.99 to 111) | 0.99(0.90 to 1.09) | 0.862 | 0.366 | 0.377 |
Plasma ouabain, plasma renin activity and urinary aldosterone excretion
Safety
Placebo | Rostafuroxin | ||||||
---|---|---|---|---|---|---|---|
All | All | 0.05 mg | 0.15 mg | 0.5 mg | 1.5 mg | 5.0 mg | |
Total number of patients | 419* | 419† | 84 | 84 | 81 | 87 | 83 |
Number with complaints | |||||||
Osteomuscular‡ | 4 | 3 | 1 | 1 | 0 | 0 | 1 |
Gastro-intestinal# | 5 | 5 | 0 | 1 | 1 | 1 | 2 |
Dizziness | 2 | 5 | 0 | 1 | 0 | 4 | 0 |
Dry mouth | 1 | 4 | 1 | 0 | 0 | 1 | 2 |
Headache | 8 | 14 | 3 | 4 | 2 | 2 | 3 |
High blood pressure | 4 | 6 | 1 | 3 | 2 | 0 | 0 |
Otitis | 1 | 2 | 0 | 1 | 1 | 0 | 0 |
Palpitations | 1 | 3 | 0 | 0 | 1 | 0 | 2 |
Cutaneous§ | 0 | 4 | 2 | 1 | 0 | 1 | 0 |
Upper respiratory tract infections | 5 | 8 | 5 | 1 | 0 | 0 | 2 |
Urinary abnormalities¶ | 0 | 5 | 2 | 0 | 2 | 1 | 0 |
Urinary tract infections | 2 | 5 | 1 | 2 | 0 | 2 | 0 |
Sensitivity analyses
Mean level ± SD at end of period | Mean differences (95% CI) |
P-value | ||||
---|---|---|---|---|---|---|
N | Baseline | 5 weeks | 5 weeks minus baseline | Double difference (rostafuroxin minus placebo) | ||
Systolic pressure, mm Hg | ||||||
Placebo | 203 | 149.8 ± 7.2 | 144.5 ± 12.5 | -5.35 (-6.97 to -3.74) | ||
Rostafuroxin | ||||||
0.05 mg | 42 | 150.5 ± 7.3 | 144.5 ± 12.6 | -6.00 (-9.86 to -2.13) | -1.20 (-6.28 to 3.87) | 0.64 |
0.15 mg | 40 | 150.5 ± 8.4 | 143.9 ± 12.4 | -6.60 (-9.91 to -3.29) | -3.08 (-8.03 to 1.88) | 0.22 |
0.5 mg | 40 | 153.0 ± 8.7 | 147.4 ± 11.5 | -5.65 (-9.42 to -1.88) | 0.96 (-4.74 to 6.66) | 0.74 |
1.5 mg | 43 | 151.0 ± 7.9 | 147.4 ± 15.2 | -3.68 (-7.87 to 0.51) | 1.59 (-3.77 to 6.95) | 0.56 |
5.0 mg | 42 | 149.6 ± 7.1 | 145.3 ± 14.0 | -4.31 (-8.55 to -0.07) | 2.45 (-3.05 to 7.95) | 0.38 |
All doses | 207 | 150.9 ± 7.9 | 145.7 ± 13.2 | -5.22 (-6.92 to -3.53) | 0.13 (-2.21 to 2.47) | 0.91 |
Diastolic pressure, mm Hg | ||||||
Placebo | 203 | 92.0 ± 7.2 | 89.4 ± 8.7 | -2.63 (-3.77 to -1.50) | ||
Rostafuroxin | ||||||
0.05 mg | 42 | 92.9 ± 7.2 | 89.9 ± 8.3 | -3.01 (-4.90 to -1.11) | 0.52 (-2.65 to 3.70) | 0.75 |
0.15 mg | 40 | 92.3 ± 7.5 | 88.5 ± 8.5 | -3.82 (-6.12 to -1.51) | -1.94 (-5.52 to 1.65) | 0.28 |
0.5 mg | 40 | 95.9 ± 6.6 | 92.0 ± 7.8 | -3.96 (-6.67 to -1.25) | -1.20 (-5.32 to 2.92) | 0.56 |
1.5 mg | 43 | 94.2 ± 8.3 | 92.9 ± 9.4 | -1.33 (-3.77 to 1.12) | -0.21 (-3.26 to 2.84) | 0.89 |
5.0 mg | 42 | 94.0 ± 6.5 | 90.7 ± 9.2 | -3.33 (-6.32 to -0.35) | 0.68 (-3.15 to 4.51) | 0.72 |
All doses | 207 | 93.9 ± 7.3 | 90.8 ± 8.7 | -3.06 (-4.15 to -1.98) | -0.43 (-2.00 to 1.13) | 0.59 |
Mean level ± SD at end of period | Mean differences (95% CI) |
P-value | ||||
---|---|---|---|---|---|---|
N | Baseline | 5 weeks | 5 weeks minus baseline | Double difference (rostafuroxin minus placebo) | ||
Systolic pressure, mm Hg | ||||||
Placebo | 189 | 137.8 ± 10.7 | 135.6 ± 12.2 | -2.28 (-3.78 to -0.77) | ||
Rostafuroxin | ||||||
0.05 mg | 39 | 137.3 ± 11.3 | 132.5 ± 11.2 | -4.74 (-8.00 to -1.48) | -1.16 (-5.38 to 3.06) | 0.59 |
0.15 mg | 36 | 134.9 ± 10.9 | 137.3 ± 11.2 | +2.36 (-0.62 to 5.34) | 3.16 (-1.32 to 7.63) | 0.16 |
0.5 mg | 38 | 137.4 ± 9.6 | 136.7 ± 9.9 | -0.76 (-4.44 to 2.92) | 2.63 (-2.44 to 7.70) | 0.30 |
1.5 mg | 40 | 137.8 ± 11.8 | 138.0 ± 10.3 | +0.21 (-3.10 to 3.51) | 2.12 (-2.74 to 6.98) | 0.39 |
5.0 mg | 36 | 136.2 ± 11.7 | 135.6 ± 11.9 | -0.52 (-4.32 to 3.27) | 1.33 (-4.00 to 6.66) | 0.62 |
All doses | 189 | 136.8 ± 11.0 | 136.0 ± 11.0 | -0.74 (-2.24 to 0.77) | 1.54 (-0.59 to 3.66) | 0.16 |
Diastolic pressure, mm Hg | ||||||
Placebo | 189 | 86.2 ± 7.8 | 84.0 ± 8.7 | -2.28 (-3.28 to -1.28) | ||
Rostafuroxin | ||||||
0.05 mg | 39 | 84.1 ± 7.2 | 82.4 ± 8.4 | -1.65 (-3.25 to -0.06) | 1.62 (-0.74 to 3.97) | 0.18 |
0.15 mg | 36 | 84.2 ± 8.4 | 84.6 ± 9.1 | +0.41 (-1.46 to 2.28) | 1.62 (-1.23 to 4.47) | 0.26 |
0.5 mg | 38 | 87.6 ± 8.8 | 85.7 ± 8.3 | -1.89 (-4.15 to 0.37) | 0.68 (-2.65 to 4.01) | 0.68 |
1.5 mg | 40 | 85.6 ± 8.4 | 85.4 ± 7.4 | -0.28 (-1.96 to 1.40) | 1.64 (-1.21 to 4.50) | 0.25 |
5.0 mg | 36 | 85.0 ± 9.0 | 85.4 ± 8.4 | +0.36 (-2.34 to 3.07) | 2.85 (-0.86 to 6.57) | 0.13 |
All doses | 189 | 85.3 ± 8.4 | 84.7 ± 8.3 | -0.63 (-1.52 to 0.26) | 1.65 (0.31 to 2.98) | 0.02 |
Mean level ± SD at end of treatment period | Mean difference (95% CI) |
P-values | |||||
---|---|---|---|---|---|---|---|
N | Placebo | Rostafuroxin | Rostafuroxin minus placebo | Treatment effect | Carryover effect | Period effect | |
Systolic pressure, mm Hg | |||||||
0.05 mg | 57 | 141.1 ± 11.8 | 145.8 ± 12.8 | 4.59 (1.43 to 7.74) | 0.005 | 0.319 | 0.174 |
0.15 mg | 41 | 140.3 ± 12.1 | 140.7 ± 13.8 | 0.26 (-4.10 to 4.61) | 0.906 | 0.312 | 0.062 |
0.5 mg | 38 | 142.1 ± 15.5 | 142.9 ± 13.4 | 0.72 (-4.01 to 5.45) | 0.759 | 0.271 | 0.530 |
1.5 mg | 41 | 140.9 ± 11.8 | 142.9 ± 12.6 | 2.02 (-1.46 to 5.51) | 0.248 | 0.414 | 0.959 |
5.0 mg | 48 | 139.1 ± 9.9 | 142.1 ± 12.9 | 2.89 (-0.54 to 6.31) | 0.096 | 0.477 | 0.113 |
All doses | 225 | 140.7 ± 12.1 | 143.0 ± 13.1 | 2.35 (0.71 to 4.00) | 0.005 | 0.674 | 0.044 |
Diastolic pressure, mm Hg | |||||||
0.05 mg | 57 | 87.4 ± 8.4 | 89.2 ± 8.5 | 1.78 (-0.45 to 4.01) | 0.115 | 0.951 | 0.417 |
0.15 mg | 41 | 88.0 ± 8.5 | 88.3 ± 9.9 | 0.29 (-2.30 to 2.88) | 0.823 | 0.836 | 0.252 |
0.5 mg | 38 | 87.8 ± 8.6 | 88.6 ± 8.2 | 0.80 (-2.61 to 4.21) | 0.636 | 0.112 | 0.873 |
1.5 mg | 41 | 88.0 ± 8.9 | 90.8 ± 6.4 | 2.82 (0.51 to 5.12) | 0.018 | 0.344 | 0.191 |
5.0 mg | 48 | 86.7 ± 8.0 | 88.4 ± 7.8 | 1.74 (-1.17 to 4.66) | 0.235 | 0.510 | 0.173 |
All doses | 225 | 87.5 ± 8.4 | 89.1 ± 8.2 | 1.53 (0.37 to 2.69) | 0.010 | 0.714 | 0.033 |
Mean level ± SD at end of treatment period | Mean difference (95% CI) |
P-values | |||||
---|---|---|---|---|---|---|---|
N | Placebo | Rostafuroxin | Rostafuroxin minus placebo | Treatment effect | Carryover effect | Period effect | |
Systolic pressure, mm Hg | |||||||
0.05 mg | 55 | 131.9 ± 10.7 | 133.9 ± 11.5 | 2.02 (-0.68 to 4.73) | 0.139 | 0.129 | 0.282 |
0.15 mg | 39 | 130.9 ± 10.7 | 131.5 ± 11.8 | 0.51 (-2.59 to 3.60) | 0.743 | 0.179 | 0.588 |
0.5 mg | 36 | 135.2 ± 9.5 | 135.2 ± 9.4 | 0.04 (-3.38 to 3.46) | 0.981 | 0.523 | 0.815 |
1.5 mg | 40 | 135.3 ± 14.0 | 137.7 ± 11.7 | 2.39 (-1.20 to 5.99) | 0.185 | 0.975 | 0.193 |
5.0 mg | 44 | 133.7 ± 10.5 | 133.0 ± 12.2 | -0.68 (-3.72 to 2.36) | 0.654 | 0.831 | 0.749 |
All doses | 214 | 133.3 ± 11.2 | 134.2 ± 11.5 | 0.91 (-0.45 to 2.28) | 0.188 | 0.598 | 0.911 |
Diastolic pressure, mm Hg | |||||||
0.05 mg | 55 | 80.4 ± 7.4 | 81.9 ± 7.8 | 1.53 (-0.22 to 3.28) | 0.085 | 0.238 | 0.436 |
0.15 mg | 39 | 81.9 ± 7.6 | 81.5 ± 8.1 | -0.42(-2.80 to 1.97) | 0.725 | 0.952 | 0.328 |
0.5 mg | 36 | 85.6 ± 7.8 | 84.2 ± 9.1 | -1.42(-3.77 to 0.94) | 0.230 | 0.803 | 0.739 |
1.5 mg | 40 | 82.5 ± 9.5 | 84.0 ± 7.7 | 1.52 (-0.42 to 3.47) | 0.121 | 0.667 | 0.463 |
5.0 mg | 44 | 82.4 ± 7.4 | 82.2 ± 6.9 | -0.16 (-2.07 to 1.75) | 0.867 | 0.719 | 0.927 |
All doses | 214 | 82.4 ± 8.0 | 82.7 ± 7.9 | 0.32 (-0.57 to 1.22) | 0.474 | 0.405 | 0.757 |