Supplemental Table 1. Univariable binary and ordinal logistic regression analyses between patient baseline characteristics and efficacy endpoints.
Independent functional outcome at 90 days
Clinical recovery at 24 h Neurological improvement at 24 h
mRS at 7 days/ discharge* mRS at 90days*
OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value cOR (95%CI) p-value cOR (95%CI) p-value Sonothrombolysis
treatment
0.98 (0.71, 1.37) 0.933 0.83 (0.60, 1.16) 0.279 1.01 (0.74, 1.39) 0.932 1.00 (0.76, 1.33) 0.987 1.00 (0.75, 1.33) 0.944 Age 0.97 (0.96, 0.99) 0.002 0.98 (0.97, 0.99) 0.035 0.99 (0.98, 1.01) 0.300 0.98 (0.96, 0.99) 0.001 0.96 (0.95, 0.98) <0.001 Baseline NIHSS 0.90 (0.86, 0.94) <0.001 0.94 (0.90, 0.98) 0.002 0.95 (0.92, 0.99) 0.007 0.83 (0.81, 0.86) <0.001 0.85 (0.82, 0.88) <0.001 Female sex 1.06 (0.76, 1.48) 0.711 0.95 (0.68, 1.32) 0.752 0.87 (0.64, 1.20) 0.404 1.30 (0.97, 1.72) 0.077 1.03 (0.78, 1.37) 0.830 SBP before tPA
bolus
0.98 (0.97, 0.99) 0.006 0.99 (0.98, 1.00) 0.111 0.99 (0.98, 0.99) 0.021 1.00 (0.99, 1.01) 0.491 1.00 (0.99, 1.01) 0.151 DBP before
alteplase bolus
1.00 (0.99, 1.01) 0.712 1.00 (0.98, 1.01) 0.722 1.00 (0.99, 1.02) 0.497 1.00 (0.99, 1.01) 0.645 1.01 (1.00, 1.02) 0.169 Serum glucose
before tPA bolus
0.98 (0.97, 0.99) 0.005 0.99 (0.98, 0.99) 0.002 0.99 (0.98, 0.99) <0.001 0.99 (0.98, 0.99) 0.001 0.99 (0.98, 1.00) <0.001 Time from
symptom onset to tPA bolus
1.00 (0.99, 1.00) 0.224 0.99 (0.99, 1.00) 0.063 1.00 (0.99, 1.01) 0.154 1.00 (0.99, 1.01) 0.298 1.00 (0.99, 1.01) 0.106
Diabetes 0.64 (0.42, 0.96) 0.030 1.01 (0.68, 1.49) 0.971 0.67 (0.46, 0.97) 0.035 0.69 (0.49, 0.96) 0.030 0.65 (0.47, 0.90) 0.010 Atrial Fibrillation 0.86 (0.57, 1.33) 0.502 1.05 (0.69, 1.62) 0.804 1.17 (0.77, 1.78) 0.452 0.70 (0.48, 1.02) 0.063 0.65 (0.45, 0.95) 0.026 Hypertension 0.63 (0.45, 0.89) 0.008 0.77 (0.55, 1.08) 0.136 0.68 (0.49, 0.94) 0.018 0.68 (0.51, 0.91) 0.008 0.59 (0.44, 0.78) <0.001 US centers 1.01 (0.61, 1.64) 0.986 1.02 (0.63, 1.65) 0.934 0.93 (0.59, 1.48) 0.769 1.03 (0.68, 1.56) 0.883 1.03 (0.67, 1.59) 0.892
Supplemental Table 2. Univariate binary and logistic regression analyses between baseline characteristics and safety endpoints.
Symptomatic ICH at 24h Symptomatic ICH at 36h Asymptomatic ICH at 24h Any ICH at 24h Mortality at 90 days OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value OR (95%CI) p-value Sonothrombolysis
treatment
1.19 (0.40, 3.58) 0.755 1.17 (0.42, 3.25) 0.767 1.85 (1.07, 3.21) 0.027 1.73 (1.05, 2.85) 0.030 1.18 (0.77, 1.82) 0.443 Age 1.00 (0.95, 1.06) 0.872 1.01 (0.96, 1.06) 0.760 1.04 (1.01, 1.07) 0.007 1.04 (1.01, 1.06) 0.011 1.07 (1.04, 1.10) <0.001
Baseline NIHSS 0.93 (0.81, 1.07) 0.319 0.93 (0.81, 1.06) 0.262 1.08 (1.02, 1.14) 0.007 1.05 (1.01, 1.11) 0.043 1.14 (1.09, 1.20) <0.001 Female sex 0.25 (0.05, 1.12) 0.071 4.81 (1.07, 21.45) 0.040 1.49 (0.85, 2.61) 0.164 0.57 (0.33, 0.96) 0.034 0.99 (0.64, 1.53) 0.961 SBP before tPA
bolus
0.99 (0.96, 1.03) 0.777 0.99 (0.97, 1.02) 0.746 1.00 (0.99, 1.02) 0.522 1.00 (0.99, 1.01) 0.632 1.00 (0.99, 1.01) 0.552 DBP before tPA
bolus
0.99 (0.94, 1.04) 0.688 0.99 (0.95, 1.03) 0.594 1.00 (0.98, 1.02) 0.811 1.00 (0.98, 1.02) 0.953 0.98 (0.97, 1.00) 0.092 Serum glucose
before tPA bolus
1.00 (0.99, 1.01) 0.874 1.00 (0.98, 1.01) 0.575 1.01 (1.00, 1.01) 0.022 1.01 (1.00, 1.02) 0.042 1.00 (1.00, 1.01) 0.009 Time from
symptom onset to tPA bolus
1.01 (0.99, 1.02) 0.168 1.01 (0.99, 1.01) 0.177 1.00 (0.99, 1.01) 0.865 1.00 (0.99, 1.01) 0.441 1.00 (0.99, 1.01) 0.556
Diabetes 1.50 (0.45, 4.94) 0.504 1.70 (0.57, 5.04) 0.341 1.49 (0.83, 2.67) 0.179 1.52 (0.89, 2.59) 0.127 1.45 (0.90, 2.34) 0.129 Atrial Fibrillation 2.18 (0.66, 7.20) 0.202 1.78 (0.55, 5.68) 0.333 1.09 (0.55, 2.16) 0.809 1.28 (0.70, 2.35) 0.425 2.13 (1.30, 3.51) 0.003 Hypertension 1.47 (0.45, 4.82) 0.526 1.80 (0.57, 5.72) 0.317 1.05 (0.61, 1.80) 0.870 1.11 (0.67, 1.84) 0.666 1.62 (1.01, 2.60) 0.045 US centers - - 0.45 (0.06, 3.48) 0.445 1.14 (0.54, 2.41) 0.722 0.89 (0.43, 1.86) 0.756 1.54 (0.85, 2.76) 0.152
*defined as functional improvement by 1-point decrease in mRS-score across all scales OR: odds ratio, cOR: common odds ratio, mRS: modified Rankin Scale, NIHSS:
National Institute of Health Stroke Scale, SBP: systolic blood pressure, DBP: diastolic blood pressure, tPA: tissue plasminogen activator
Supplemental Table 3. Adjusted sensitivity analyses of the associations between presence and number of elevated blood pressure (BP) excursions with safety and efficacy endpoints.
BP excursion presence Number of BP excursions**
Number of systolic BP excursions**
Number of diastolic BP excursions**
OR/cOR (95%CI)
p-value OR/cOR (95%CI)
p-value OR/cOR (95%CI)
p-value OR/ cOR (95%CI)
p-value Independent functional outcome
at 90 days
0.68 (0.46, 0.99) 0.048 0.87 (0.80, 0.96) 0.004 0.84 (0.75, 0.95) 0.005 0.89 (0.74, 1.08) 0.238 Clinical recovery at 24 h 0.61 (0.42, 0.89) 0.011 0.87 (0.80, 0.96) 0.005 0.84 (0.74, 0.95) 0.006 0.91 (0.76, 1.10) 0.349 Neurological improvement at 24 0.59 (0.42, 0.84) 0.004 0.87 (0.81, 0.94) <0.001 0.85 (0.78, 0.93) 0.001 0.86 (0.73, 1.02) 0.093
hours
mRS at 7 days/ discharge* 0.75 (0.55, 1.03) 0.074 0.92 (0.87, 0.97) 0.002 0.91 (0.85, 0.97) 0.003 0.91 (0.79, 1.04) 0.165 mRS at 90 days* 0.73 (0.54, 0.99) 0.044 0.93 (0.88, 0.98) 0.010 0.93 (0.87, 0.99) 0.016 0.91 (0.79, 1.05) 0.202 Symptomatic ICH at 24 hours 1.32 (0.42, 4.15) 0.634 0.99 (0.79, 1.23) 0.914 0.81 (0.48, 1.36) 0.428 1.31 (0.95, 1.81) 0.094 Symptomatic ICH at 36 hours 1.39 (0.48, 4.01) 0.546 0.99 (0.80, 1.21) 0.900 0.77 (0.45, 1.35) 0.368 1.33 (0.99, 1.79) 0.062 Asymptomatic ICH at 24 hours 1.32 (0.74, 2.34) 0.347 1.06 (0.96, 1.16) 0.256 1.03 (0.91, 1.16) 0.641 1.24 (0.99, 1.55) 0.055 Any ICH at 24 hours 1.35 (0.81, 2.27) 0.250 1.04 (0.96, 1.14) 0.337 0.99 (0.88, 1.12) 0.939 1.30 (1.07, 1.58) 0.009 90 day mortality 1.05 (0.64, 1.70) 0.855 1.02 (0.93, 1.11) 0.651 1.00 (0.90, 1.11) 0.999 1.15 (0.92, 1.43) 0.212
*defined as functional improvement by 1-point decrease in mRS-score across all scales, **ORs and cORs presented per 1 unit increase.
NIHSS: National Institutes of Health Stroke Scale, mRS: modified Rankin Scale, ICH: intracranial hemorrhage.
All analyses were adjusted for age, baseline NIHSS score, glucose on admission and time from stroke onset to tissue plasminogen activator bolus.
Supplemental Table 4. Adjusted sensitivity analyses on the association between elevated blood pressure (BP) excursions burden with safety and efficacy endpoints.
BP excursions burden* Systolic BP excursions burden* Diastolic BP excursions burden * OR/cOR (95%CI)** p-value OR/cOR (95%CI)** p-value OR/ cOR (95%CI)** p-value Independent functional
outcome at 90 days
0.99 (0.71, 1.02) 0.087 0.78 (0.62, 0.97) 0.028 0.89 (0.69, 1.15) 0.369 Clinical recovery at 24 h 0.78 (0.65, 0.92) 0.004 0.71 (0.57, 0.88) 0.002 0.84 (0.65, 1.09) 0.186 Neurological improvement
at 24 hours
0.83 (0.70, 0.97) 0.022 0.76 (0.63, 0.92) 0.005 0.85 (0.67, 1.07) 0.168 mRS at 7 days/
discharge***
0.85 (0.75, 0.98) 0.026 0.82 (0.69, 0.96) 0.013 0.90 (0.74, 1.10) 0.314 mRS at 90 days*** 0.85 (0.75, 0.97) 0.018 0.85 (0.73, 0.99) 0.033 0.85 (0.69, 1.04) 0.125 Symptomatic ICH at 24
hours
1.14 (0.71, 1.81) 0.581 0.83 (0.41, 1.67) 0.598 1.62 (0.96, 2.73) 0.070 Symptomatic ICH at 36 1.16 (0.75, 1.78) 0.502 0.77 (0.38, 1.56) 0.467 1.68 (1.04, 2.72) 0.033
hours
Asymptomatic ICH at 24 hours
1.12 (0.88, 1.42) 0.346 1.09 (0.83, 1.43) 0.537 1.28 (0.91, 1.80) 0.152 Any ICH at 24 hours 1.13 (0.89, 1.44) 0.307 1.11 (0.84, 1.46) 0.463 1.27 (0.91, 1.78) 0.164 90 day mortality
*as categorical variables (0, 1, 2, 3-), **ORs and cORs presented per 1 unit increase, ***defined as functional improvement by 1-point decrease in mRS-score across all scales, NIHSS: National Institutes of Health Stroke Scale, mRS: modified Rankin Scale, ICH: intracranial hemorrhage.