Table 5.
Stage 2 Clinical Outcomes (mITT Population)
| Placebo | Otaplimastat 40 mg | Otaplimastat 80 mg | |||||
|---|---|---|---|---|---|---|---|
| Median [IQR] | Median [IQR] | p | OR (95% CI) Adjustedp | Median [IQR] | p | OR (95% CI) Adjusted p | |
| Evaluable, na | 22 | 22 | 21 | ||||
| mRS | |||||||
| mRS at day 0 | 4 [3 to 4] | 4 [3 to 4] | 0.833 | 4 [3 to 4] | 0.192 | ||
| mRS at day 90 | 1.0 [1.0 to 1.0] | 0.0 [0.0 to 2.0] | 0.026 | OR 3.2 (0.9 to 10.9)b p = 0.068b | 1.0 [0.0 to 3.0] | 0.502 | OR 2.0 (0.6 to 6.7)b p = 0.246b |
| NIHSS changes | 0.006c | 0.940c | |||||
| Baseline at day 0 | 8.0 [5.0 to 14.0] | 11.0 [5.0 to 15.0] | >0.999 | 9.0 [5.0 to 13.0] | >0.999 | ||
| Changes at day 5 | −4.0 [−8.0 to −1.5] | −7.0 [−11.0 to −4.5] | 0.387 | −4.0 [−9.0 to −2.0] | 0.866 | ||
| Changes at day 28 | −4.0 [−9.0 to −3.0] | −7.0 [−11.5 to −5.0] | 0.234 | −5.5 [−10.0 to −2.0] | 0.922 | ||
| Changes at day 90 | −5.0 [−10.0 to −4.0] | −8.0 [−11.0 to −5.0] | 0.414 | −7.0 [−10.0 to −5.0] | 0.880 | ||
| Infarct growth, mld | |||||||
| Baseline at day 0 | 4.9 [0.5 to 8.1] | 5.9 [0.9 to 24.0] | 0.579 | 3.2 [0.7 to 15.6] | 0.982 | ||
| Growth at day 5 | 3.2 [0.3 to 7.9] | 1.7 [0.0 to 11.1] | >0.999 | 3.0 [0.5 to 9.0] | 0.866 | ||
| Fold change in 5 days | 0.7 [0.1 to 1.6] | 0.1 [0.0 to 0.9] | 0.303 | 0.3 [0.0 to 0.8] | 0.423 | ||
The mITT population is defined as the population composed of all subjects who belonged to the safety analysis set, fulfilled major inclusion/exclusion criteria, and had at least 1 post‐treatment assessment with primary endpoint. A total of 4 patients missed primary computed tomography outcome analysis and were excluded: 2 in the placebo group (1 transient ischemic attack, 1 death at day 1), and 2 in the 40 mg otaplimastat group (2 withdrew, 1 each at days 0 and 5). Analysis uses observed data. Probability value was obtained by Mann–Whitney test or Fisher exact test at each time point, with multiplicity adjustment by Holm–Bonferroni correction.
mRS at day 90: placebo, n = 21; otaplimastat 40 mg, n = 20; 80 mg, n = 20. NIHSS: placebo, n = 22; otaplimastat 40 mg, n = 22; 80 mg, n = 21 at day 0. Placebo, n = 20; otaplimastat 40 mg, n = 20; 80 mg, n = 19 at day 5 and day 28. Placebo, n = 19; otaplimastat 40 mg, n = 17; 80 mg, n = 17 at day 90. Infarct growth from day 0 to day 5: placebo, n = 20; otaplimastat 40 mg, n = 20; 80 mg, n = 19.
Ordinal logistic regression analysis for mRS distribution (mRS = 0–6) at day 90 uses imputed data for death cases. Unadjusted probability values are: p = 0.257 for placebo vs 40 mg and p = 0.674 for placebo vs 80 mg. Adjusted probability values and ORs show the effect of treatment, adjusted for age, sex, baseline NIHSS, tissue plasminogen activator treatment time after stroke onset, and the use of endovascular surgery.
Changes in NIHSS scores were analyzed with the van Elteren test.
Measurement of infarct growth by diffusion‐weighted imaging on days 0 and 5 (edema unadjusted). Infarct growth on day 5 = individual infarct volume on day 5 − individual infarct volume on day 0. Fold change of infarct growth = infarct growth on day 5 / mean of infarct volumes on day 0.
CI = confidence interval; IQR = interquartile range; mITT = modified intention‐to‐treat; mRS = modified Rankin scale; NIHSS = National Institutes of Health Stroke Scale; OR = odds ratio.