The primary objective of this randomized controlled trial is to determine whether decompressive surgery and best medical treatment in patients with spontaneous ICH will improve outcome compared to best medical treatment only. Secondary objectives…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Nervous system, skull and spine therapeutic procedures
- Vascular haemorrhagic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the composite of mortality or dependency (mRS score 5
[severe dependency] or 6 [death]) at 180 days ± 14 days. Primary endpoint (mRS)
will be assessed by a structured telephone interview (180 days ± 14 days post
randomization)
Secondary outcome
Composite of mortality or dependency
- mRS score 5 [severe dependency] or 6 [death]) at 30 ± 7 days by telephone
interview.
Mortality
- Mortality will be assessed by using the mRS at 7 days (if discharged earlier,
this will be assessed at discharge), 30 ± 7 days, 180 ± 14 days and at 12
months ± 30 days by telephone interview. If patients/relatives do not respond
the general practitioner or treating physician will be contacted.
Dependency
- Dependency is assessed using the mRS at 7 days (if discharged earlier, this
will be assessed at discharge), 30 ± 7 days, 180 ± 14 days and at 12 months ±
30 days by telephone interview.
mRS score of 0-3 versus 4-6, at 30 ± 7 days, at 180 ± 14 days and at 12 months
± 30 days
- This is a secondary analysis of the mRS.
Categorical shift in modified Rankin Scale (mRS) score at 180 ± 14 days
- This is a secondary analysis of the mRS.
QoL:
- QoL will be assessed at 180 ± 14 days and at 12 months ± 30 days after
randomization using the EuroQoL questionnaire. It will be assessed during a
telephone interview.
National Institutes of Health Stroke Scale (NIHSS)
- NIHSS will be assessed at baseline, at 7 days (if discharged earlier, this
will be assessed at discharge) and 180 ± 14 days, by a trained neurologist or
trial nurse.
Glasgow Coma Scale (GCS)
- The GCS will be assessed at baseline, at discharge and during an outpatient
visit 180 ± 14 days after randomization by a trained neurologist or trial nurse.
Length of hospital stay
- Hospitalization will include only the initial hospitalization and treatment.
Assessment is based on medical records and will be performed 6 months after
study inclusion.
Residential care
- The status of residential care will be assessed based on medical records and
questioning of the patient and/or relatives at 180 ± 14 days and at 12 months
by telephone interview.
Safety
- Safety outcomes will be evaluated according to the details given in Section
10 of the study protocol.
Size of infarction
- The size of infarction/brain damage will be measured volumetrically in the
imaging core lab using the 6 month imaging (CT/MRI). Therefore, the
pseudo-anonymized CT/MRI scan of visit 7 will be sent on CD-ROM to the trial
coordinator.
Time from symptom onset to randomization
- Onset of symptoms and time of randomization are retained (date and time) in
the case report form (CRF).
Radiological outcome measures
- The midline shift will be centrally assessed and reviewed in the imaging core
lab using the pre-randomization imaging (CT/MRI). Therefore the
pseudo-anonymized CT/MRI scan of visit 1 will be sent on CD-Rom to the trial
coordinator.
- Hematoma enlargement
- Presence of spot sign on brain imaging
Surgical procedure
- EVD
- ICP
- CSF shunt
- DC
- Surgical removal of hematoma
Background summary
Spontaneous intracerebral hemorrhage (ICH) remains a devastating disease with
mortality rates up to 52% at 30 days. It is a major public health
problem with an annual incidence of 10-30 per 100*000 population, accounting
for 2 million (10-15%) of about 15 million strokes worldwide each year. The
strategy of decompressive craniectomy (DC) is beneficial in patients with
malignant middle cerebral artery (MCA) infarction. Based on
the common pathophysiological mechanisms of these two conditions, this
procedure is also frequently performed in patients with ICH, but is has not yet
been investigated in a randomized trial.
Study objective
The primary objective of this randomized controlled trial is to determine
whether decompressive surgery and best medical treatment in patients with
spontaneous ICH will improve outcome compared to best medical treatment only.
Secondary objectives are to analyze mortality, dependency and quality of life.
Safety endpoints are to determine cause of any mortality and the rate of
medical and surgical complications after DC compared with best medical
treatment alone.
Study design
Multicenter randomized (1:1) controlled, parallel group trial
Intervention
All patients in the treatment group will receive decompressive hemicraniectomy
with a diameter of at least 12 cm and best medical treatment according to
institutional guidelines and a surgical protocol.
Study burden and risks
The role of hematoma evacuation in the treatment of ICH is still unclear, and
it is also unknown whether decompressive craniectomy (DC) in the treatment of
ICH is beneficial, even though DC is a standard approach in patients with
malignant MCA infarction and in patients with ICH due to sinus venous
thrombosis, herpes encephalitis and brain trauma. According to the literature,
DC in conjunction with hematoma evacuation improved outcome, yet the reported
DCs did not achieve modern standards and hematoma evacuation for deep seated
hematoma has not been proven beneficial for the patient. The Bern researchgroup
analyzed DC in ICH in a recent retrospective series and showed a reduced
mortality, but no statistically significant improvement of outcome at 3 months
according to the mRS. However, this retrospective trial was underpowered to
show a potential benefit; there was no difference between the surgical and
conservative groups. Despite this lack of statistical significance, a potential
benefit for patients was the increased survival rate without serious
complications; surgery was not associated with a higher rate of mortality or
morbidity. After these results were published one new pre-clinical trial, one
meta-analysis, and one original contribution were published, all dealing with
DC in ICH without hematoma evacuation. All studies came to the conclusion that
the risk/benefit ratio is favorable and mandates a randomized controlled trial.
DC is a standard approach and risks associated with DC are well known. It is a
comparatively simple procedure that is performed in every neurosurgical center.
Guresir et al. investigated the rate of complications in DC; their analysis
distinguished between complications related to the DC and those related to
cranioplasty. The most common complications related to DC were wound healing
disturbances (3.5%), abscess (2.6%), CSF fistula (0.6%) and epi/subdural
hematoma (2.1%). Complications related to cranioplasty were wound healing
disturbances (6.1%), abscess (2.6%), CSF fistula (1%), epi/subdural hematoma
(4.1%), hygroma (1.5%) and bone flap dislocation (0.5%).
Freiburgstrasse 1
Bern 3010
CH
Freiburgstrasse 1
Bern 3010
CH
Listed location countries
Age
Inclusion criteria
- Age: >=18 to <=75 years
- Deep ICH (basal ganglia or thalamus) that may extend into cerebral lobes,
ventricles or subarachnoid space
- Acute stroke syndrome due to a spontaneous ICH
- NIHSS score of >=10 and <=30
- Glasgow coma scale (GCS) >7 and <14
- Randomization within 66 hours after ictus
- Surgical treatment not later than 6 hours after randomization
- Volume of hematoma >=30 ml and <=100 ml
Exclusion criteria
- ICH due to known or suspected structural abnormality in the brain (e.g.,
intracranial aneurysm, brain arteriovenous malformation, brain tumor) or brain
trauma, or previous stroke thrombolysis
- Cerebellar or brainstem hemorrhage
- Exclusive lobar hemorrhage
- Moribund patients (GCS 3-7)
- Patient has a signed do-not-treat statement
- Known advanced dementia or significant pre-stroke disability
- Concomitant medical illness that would interfere with outcome assessment and
follow-up
- Pregnancy
- Prior major brain surgery within <6 month or prior DC
- Foreseeable difficulties in follow-up due to geographic reasons
- Known definite contraindication for a surgical procedure
- A very high likelihood that the patient will die within the next 24 hours on
the basis of clinical and/or radiological criteria
- Previous participation in this trial or in another ongoing investigational
trial
- Prior symptomatic ICH
- ICH secondary to thrombolysis
- Bilateral areactive pupils
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02258919 |
| CCMO | NL53420.041.15 |