Table 2.
Primary and secondary outcomes
| Placebo (n = 118) | Valproic acid (n = 126) | Risk difference* (95% CI) | Relative risk* (95% CI) | P | |
|---|---|---|---|---|---|
| Primary outcome† | |||||
| Intention to treat | 72/118 (61%) | 77/126 (61%) | + 2.5% (− 6.3 to 11.2) | 1.04 (0.90 to 1.20) | 0.58 |
| Worst-case scenario | 73/118 (62%) | 77/126 (61%) | + 1.8% (− 7.5 to 11.1) | 1.03 (0.88 to 1.20) | 0.70 |
| Available data | 72/117 (62%) | 77/125 (62%) | + 2.6% (− 7.3 to 12.5) | 1.04 (0.89 to 1.23) | 0.60 |
| Secondary outcomes | |||||
| Refractory status epilepticus | 6/118 (5%) | 5/126 (4%) | − 0.9% (− 5.6 to 3.8) | 0.82 (0.32 to 2.08) | 0.68 |
| Super-refractory status epilepticus | 4/118 (3%) | 3/126 (2%) | − 1.0% (− 5.7 to 3.7) | 0.71 (0.17 to 2.96) | 0.64 |
| Recurrence of seizure during ICU stay‡ | 14/118 (12%) | 7/125 (6%) | − 6.1% (− 15.2 to 3.0) | 0.48 (0.23 to 1.00) | 0.049 |
| Time to awakening (hours) | 18 (9–72) [n = 117] | 24 (12–72) | |||
| [n = 121] | – | 0.84 (0.64 to 1.10)§ | 0.21 | ||
| Length of ICU stay (days) | 4 (3–7) | 5 (3–8) | – | 0.91 (0.70 to 1.18)§ | 0.46 |
| Length of hospital stay (days) | 11 (7–23) | 12 (7–24) | – | 0.97 (0.75 to 1.27)§ | 0.84 |
| Highest SOFA score¶ | 4 (2–7) [n = 76] | 4 (2–6) [n = 74] | + 0.2 (− 0.9 to 1.4) ‖ | – | 0.68 |
| Death in ICU | 2/118 (2%) | 4/126 (3%) | + 1.6% (− 2.5 to 5.8) | 1.99 (0.48 to 8.27) | 0.35 |
| Death in hospital | 2/118 (2%) | 7/126 (6%) | + 4.0% (− 0.7 to 8.7) | 2.94 (0.61 to 14.3)§ | 0.18 |
| Death from randomisation to day 90 | 3/118 (3%) | 8/126 (6%) | + 4.7% (− 1.9 to 11.3) | 2.32 (0.61 to 8.84)** | 0.22 |
| MMSE score at day 90 | 26 (21–29) [n = 21] | 26 (23–28) [n = 18] | − 0.2 (− 4.7 to 4.2) ‖ | – | 0.92 |
| FAB score at day 90 | 14 (12–17) [n = 26] | 15 (12–18) [n = 23] | + 0.2 (− 2.1 to 2.5) ‖ | – | 0.16 |
| Glasgow Outcome Score at day 90 | 5 (4–5) [n = 44] | 4 (3–5) [n = 55] | – | 0.71 (0.33 to 1.58)†† | – |
Data are n/N (%) or median (first–third quartile) unless otherwise stated
* Adjusted for randomisation strata (age ≤ 65 or > 65 years, and presence or absence of acute brain injury), and centre
† Defined by the proportion of patients discharged alive from hospital to their home or to a long-term care facility on day 15
‡ Defined by the recurrence of seizure or status epilepticus in patients for whom GCSE has been controlled
§ Adjusted sub-distribution hazard ratio
¶ Worst score day 2 to day 15
‖ Adjusted mean difference
** Adjusted hazard ratio
†† Adjusted odds ratio estimated in a Bayesian proportional odds model; no P-value is computed
CI Confidence interval; FAB Frontal Assessment Battery [38]; ICU Intensive care unit; MMSE Mini-Mental State Examination [39]; SOFA Sepsis-related Organ Failure Assessment