Dexamethasone (DXM) therapy in symptomatic patients with chronic subdural hematoma (DECSA- Trial). Effect of initial corticosteroid therapy versus primary surgery on clinical outcome.

Chronic subdural haematoma (CSDH) is a common neurological disease with a
rapidly rising prevalence due to increasing age and widespread use of (oral)
anti-coagulant agents (OAC). Surgical intervention by burr hole craniotomy
(BHC) is the treatment of choice in symptomatic patients. In several hospitals
however, dexamethasone (DXM) therapy is administered as an alternative,
non-surgical treatment. The reasoning is that surgery may be associated with
complications, recurrence rates up to 30%, and mortality. Moreover, advanced
age, presence of comorbidities and use of anti-coagulant agents could impede
an operation. However, the use of DXM treatment is based on results of a few
small, mainly retrospective, studies of low quality due to selection bias in
patient population. In addition, treatment with DXM is of a longer duration
(days to weeks) before a possible effect on clinical outcome could me observed.
This is in contrast to the effect of surgery by burrhole craniostomy, which is
thought to have a faster effect on clinical outcome due to direct drainage of
the hematoma. High quality data is lacking and a randomized controlled trial is
necessary to evaluate the effect of DXM therapy compared to surgery on
clinical outcome. The results of this study will lead to an improved treatment
of patients with a chronic subdural hematoma.

Primary objective: To assess the effect-of initial DXM therapy versus primary
surgery on functional outcome (as expressed by the mRS) and costs in patients
with a newly diagnosed CSDH respectively after 3 and 12 months.

Secondary objectives are: Clinical outcome at discharge, after 2 weeks, 3 and
12 months, failure of therapy within 12 months after randomization (confirmed
by CT or MRI scan) and requiring intervention, clinical outcome at discharge, 2
weeks, 3, 6 and 12 months (expressed by mRS and MGS), evaluation of the quality
of life (at 3 and 12 months), haematoma recurrence (in 12 months) and haematoma
thickness (after 2 weeks), MRI-characteristics, cognitive function,
inflammatory markers and coagulation factors in subdural fluid and blood,
complications, mortality, drug related adverse events (within 3 months),
duration of hospital stay and medical- en productivity costs.

This is a prospective, randomized, controlled trial, comparing 2 different
treatment strategies in symptomatic patients (as expressed by Markwalder
grading Scale score of 1-3) with a chronic subdural hematoma (CSDH): initial
dexemathason (DXM) therapy versus primary surgery (by burr hole craniostomy,
current standard practice in symptomatic patients). The study is designed to
evaluate the effect of initial DXM therapy on functional outcome compared to
primary surgery.

Patients will be recruited for the study (after informed consent) from the
emergency department or neurological or neurosurgical outpatient clinic or ward
of partcipating hospitals. The participating neurosurgical centres are the
Haaglanden Medical Centre (HMC) at The Hague, Haga Teaching Hospital at The
Hague, Leiden University Medical Centre (LUMC) at Leiden, Medisch Spectrum
Twente (MST) in Enschede, Erasmus Medical Centre (EMC) in Rotterdam, Isala
Hospital Zwolle, University Medical Centre Groningen (UMCG) at Groningen and
Elisabeth-Tweesteden Hospital (ETZ) at Tilburg.

Patients will be evaluated during their hospital stay, at discharge, after 2
weeks combined with a follow up cranial CT at the outpatient clinic and after 3
months at the outpatient clinic. Patients will also be evaluated by phone after
3, 6 and 12 months. Patients will also be requested to fill in questionnaires
regarding their quality of life and the cost effectiveness at 3 and 12 months.

If patients are eligible for the MRI-substudy, one MRI-scan of the brain will
be performed (after receiving additional informed consent).
If patients agree to (give consent for) the storage of subdural fluid and blood
when the have an operation (as the primary treatment or as additional treatment
when DXM therapy is not sufficient), this will be stored for analyses.
To achieve an inclusion of 420 patients (210 patients in each subject group),
we will allow 3 years for this study.

The intervention group consists of patients randomised for the dexamethasone
treatment. This intervention group will be compared to the control group, that
will receive the current standard therapy, which is primary surgery by means of
burr hole craniostomy.

The intervention group (dexamethason-group) will receive a daily dose of 16 mg
DXM (8 mg every 12 hours) on day 1 to 4. Thereafter, DXM will be tapered down
by halve every 3 days (4 mg every 12 hours on day 5 to 7, 2 mg every 12 hours
on day 8 to 10, 1 mg every 12 hours on day 11 to 13, 0.5 mg every 12 hours on
day 14 to 16 and 0.5 mg once a day on day 17 to 19). DXM is administered orally
in tablets or intravenously when oral administration is not possible due to the
clinical condition of the patient.

If the patient improves on DXM therapy (expressed by >= 1 point decrease in MGS
and >= 1 point increase in GCS), the treatment can be continued and completed
until day 19. There are however a few scenarios in which the treating physician
can decide to discontinue DXM therapy:; these are described in paragraph 8.3
(study procedures) of the study protocol.

Risk assessment of the study:

We expect that the risks are no higher for patients participating in the study
than patients in the regular setting outside of the study, since both
treatments (DXM or surgery) are already being used in current clinical
practice. In this study we merely randomize the treatment in order to achieve
more clarity about the effects of DXM compared to surgery on the clinical
outcome of the patient. Surgery can be performed at any time, if the patient
does not respond sufficient to DXM therapy. The patient is therefore not
exposed to a greater risk than outside of the study setting.

Assessment of the burden of the study:

All physical examination (neurological examination) that is performed, blood
tests and the cranial CT scan are part of current routine medical care of
patients with cerebral hemorrhage, so there will be no extra burden for the
patient. The follow-up evaluation at the outpatient clinic at 2 weeks (with
follow-up cranial CT scan) and at 3 months are also part of routine (standard)
medical care. Follow-up evaluation by phone at 3, 6 and 12 months are an extra
evaluation and might therefore be experienced as a burden, as well as
completing the questionnaires on quality of life and cost-effectiveness (after
3 and 12 months). Finally, the MRI-scan which will be performed once in
patients that have given consent for the MRI-substudy is also an additional
evaluation. The KCL-substudy will not be an extra burden for the patient.

The benefit of this study is however, that we gain more clarity on evidence
based treatment for future patients with a similar condition.