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).

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.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Statistical analysis plan for the Dex-CSDH trial: a randomised, double-blind, placebo-controlled trial of a 2-week course of dexamethasone for adult patients with a symptomatic chronic subdural haematoma.

BACKGROUND: The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the 6-month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate. METHODS AND DESIGN: Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0-3) versus unfavourable (a score of 4-6). CONCLUSIONS: This paper and the accompanying additional material describe the statistical analysis plan for the trial. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015.

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions. METHODS: Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis. DISCUSSION: This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810 . Registered on 7 November 2014. EudraCT, 2014-004948-35 . Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.