A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Abstract

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases.

Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma.

Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation.

Setting: Neurosurgical units in the UK.

Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging.

Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care.

Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year.

Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19.

Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group.

Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study.

Trial registration: This trial is registered as ISRCTN80782810.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.