Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH[Trauma]): The First Randomized Trial

Abstract

Intraparenchymal hemorrhages occur in a proportion of severe traumatic brain injury TBI patients, but the role of surgery in their treatment is unclear. This international multi-center, patient-randomized, parallel-group trial compared early surgery (hematoma evacuation within 12 h of randomization) with initial conservative treatment (subsequent evacuation allowed if deemed necessary). Patients were randomized using an independent randomization service within 48 h of TBI. Patients were eligible if they had no more than two intraparenchymal hemorrhages of 10 mL or more and did not have an extradural or subdural hematoma that required surgery. The primary outcome measure was the traditional dichotomous split of the Glasgow Outcome Scale obtained by postal questionnaires sent directly to patients at 6 months. The trial was halted early by the UK funding agency (NIHR HTA) for failure to recruit sufficient patients from the UK (trial registration: ISRCTN19321911). A total of 170 patients were randomized from 31 of 59 registered centers worldwide. Of 82 patients randomized to early surgery with complete follow-up, 30 (37%) had an unfavorable outcome. Of 85 patients randomized to initial conservative treatment with complete follow-up, 40 (47%) had an unfavorable outcome (odds ratio, 0.65; 95% confidence interval, CI 0.35, 1.21; p=0.17), with an absolute benefit of 10.5% (CI, -4.4-25.3%). There were significantly more deaths in the first 6 months in the initial conservative treatment group (33% vs. 15%; p=0.006). The 10.5% absolute benefit with early surgery was consistent with the initial power calculation. However, with the low sample size resulting from the premature termination, we cannot exclude the possibility that this could be a chance finding. A further trial is required urgently to assess whether this encouraging signal can be confirmed.

Keywords: controlled trial; craniotomy; intracerebral hemorrhage; randomized; traumatic brain injury.

FIG. 1.

Flow chart for STITCH(Trauma) patients. *One site recruited 1 patient, but had undertaken surgery before randomization—the patient was allocated to initial conservative treatment; another site recruited 1 patient, for whom a treatment decision not to operate was made before the patient was randomized—this patient was allocated to early surgery. Because of the severe breach of protocol, these patients were excluded.

FIG. 2.

Outcome at 6 months. Statistical significance tests for outcome. (A) Proportional odds model, p=0.153; chi-squared for trend, p=0.047; outcome. (B) Proportional odds model, p=0.127; chi-squared for trend, p=0.052; outcome. (C) Proportional odds model, p=0.147; chi-squared for trend, p=0.043. ES, early surgery; ICT, initial conservative treatment.

FIG. 3.

Kaplan-Meier's survival analysis. Log-rank test, p=0.0081.

FIG. 4.

Subgroup analysis. M-H, Mann-Whitney; CI, confidence interval; GCS, Glasgow Coma Score.