Clinical trial NCT02258919: Decompressive Hemicraniectomy in Intracerebral Hemorrhage
Official title: Swiss Trial of Decompressive Craniectomy Versus Best Medical Treatment of Spontaneous Supratentorial Intracerebral Hemorrhage (SWITCH): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cerebral Hemorrhage
Keywords: Intracerebral hemorrhage
Decompressive craniectomy
Randomized controlled trial
Acute stroke
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2014-10-08
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Detailed description: Background

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. One-third of patients with ICH die within one month and the majority of survivors remain handicapped. Neurological injury resulting from ICH is mediated by the mass effect of the hematoma, secondary to brain edema and/or both mechanisms. Treatment of ICH is one of the major unresolved issues of acute stroke treatment. The International Surgical Trials in Intracerebral Hemorrhage (STICH and STICH II) and other randomized controlled trials did not show any superiority of surgical treatment compared to conservative treatment approaches. Nevertheless, surgical treatment in ICH remains a matter of debate and attempts to improve outcome using surgical therapy are still ongoing. Many efforts are made to minimize the invasiveness of operative procedures such as clot evacuation. However, direct surgical interventions aiming at the removal of the hematoma have failed to improve neurological outcome for most subtypes of ICH, especially deep-seated hematomas. The trauma of open craniotomy and especially trauma to the brain parenchyma for hematoma evacuation are considered to outweigh the benefits of surgery.

Decompressive craniectomy (DC), which is beneficial in patients with malignant middle cerebral artery (MCA) infarction, may indirectly relieve the mass effect, decrease perihematomal tissue pressure, improve blood flow, reduce secondary brain damage and improve outcome without further damage to the brain due to surgery. Consequently, DC has been established as a standard surgical therapy for patients with malignant MCA infarction with a level of evidence grade 2. Decompressive craniectomy for acute stroke is one of the most effective treatments available: the number needed to be treated to save one patient's life is 2. Decompressive craniectomy is also a standard therapeutic procedure in patients with ICH due to sinus venous thrombosis, herpes encephalitis, or ruptured intracranial aneurysms. In patients with traumatic brain injury DC is a standard therapy to reduce elevated intracranial pressure. The investigators and others assessed whether DC is feasible and beneficial in patients with spontaneous intracranial hemorrhage. The investigators showed in a previous retrospective trial that DC in patients with supratentorial ICH is safe and feasible and may reduce mortality compared to matched controls with best medical treatment alone. The limitations of the feasibility trial are its retrospective design, the small sample size and the inhomogeneity of the patient cohort with respect to the origin of ICH. Furthermore, in the feasibility trial the decision for DC was taken on an individual basis rather than according to a strict protocol, introducing a potential selection bias. Nevertheless, the preliminary results are encouraging. Recently, three human trials, one animal study, one meta-analysis, and one original contribution have been published on this topic. However, no prospective randomized trial has ever assessed whether DC without hematoma evacuation in patients with acute ICH improves outcome. All recent studies showed promising results and all call for the initiation of a randomized controlled trial.

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.

Methods

All patients with a suspected intracerebral hemorrhage will be considered for this trial. Randomization of eligible patients will be performed within 66 hours after ictus in patients with stable clot volume and surgery no later than 6 hours after randomization. Patients randomized to the control group will receive best medical treatment according to international guidelines. Patients randomized to the treatment group will receive best medical treatment and a DC of at least 12cm according to institutional guidelines and a surgical protocol. The primary outcome death and dependency at 6 months will be assessed by a trained person unaware of treatment allocation. Favorable outcome is defined as a modified Rankin Scale (mRS) score of 0 to 4, poor outcome as modified Rankin Scale score of 5 or 6.

Eligibility criteria: Inclusion Criteria:

* Written informed consent of the patient or of patient's next of kin plus consent of an independent physician if patient is unable to consent before randomization
* Acute stroke syndrome due to a spontaneous ICH, defined as the sudden occurrence of bleeding into the parenchyma of the basal ganglia and/or thalamus that may extend into the ventricles and into the cerebral lobes, and into the subarachnoid space, confirmed by clinical history and imaging
* Age: ≥18 to ≤75 years
* Glasgow coma scale (GCS) \<14 and \>7
* Neurological deficit with a NIHSS score of ≥10 and ≤30
* Able to be randomly assigned to surgical treatment within 66 hours after ictus
* Surgery performed not later than 6 hours after randomization
* Volume of hematoma ≥30 ml and ≤100 ml
* Stable clot volume
* International normalized ratio (INR) \<1.5, thrombocytes \>100 T/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
* Known advanced dementia or significant pre-stroke disability
* Concomitant medical illness that would interfere with outcome assessment and follow-up
* Randomization not possible within 66 hours after ictus
* 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

Primary outcomes:
measure: Score in modified Rankin Scale (mRS)
timeFrame: 6 months
Secondary outcomes:
measure: Mortality
timeFrame: 7 days, 30 days, 180 days, 12 months
measure: mRS score of 0-3 versus 4-6
timeFrame: 30 days, 180 days, 12 months
measure: Categorical shift in mRS score
timeFrame: 180 days, 12 months
measure: Quality of life
timeFrame: 180 days, 12 months
measure: Death and intracranial hemorrhage
timeFrame: intraoperative
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Universitätsklinik für Neurochirurgie, Kepler Universitätsklinikum Linz
city: Leuven
country: Belgium
facility: UZ Leuven
city: Helsinki
country: Finland
facility: Department of Neurology, Helsinki University Central Hospital
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
city: Paris
country: France
facility: Fondation Adolphe de Rothschild
city: Lübeck
country: Germany
facility: Klinik für Neurochirurgie, Universitätsklinikum Schleswig Holstein
state: Schleswig Holstein
city: Erfurt
country: Germany
facility: Klinik für Neurochirugie, Helios Klinikum Erfurt
state: Thüringen
city: Aachen
country: Germany
facility: Klinik für Neurochirurgie Uniklinik RWTH Aachen
city: Berlin
country: Germany
facility: Department of Neurosurgery, Charité - Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Bonn
city: Düsseldorf
country: Germany
facility: Klinik für Neurochirurgie, Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Neurologische Klinik, Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Klinik für Neurochirurgie, Universitätsklinikum Essen (AöR)
city: Frankfurt
country: Germany
facility: Zentrum der Neurologie und Neurochirurgie, Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Klinik für Neurochirurgie, Universitätsklinikum Freiburg
city: Gießen
country: Germany
facility: Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg UKGM
city: Göttingen
country: Germany
facility: Klinik für Neurochirurgie, Universitätsmedizin Göttingen
city: Kassel
country: Germany
facility: Klinik für Neurochirurgie, Klinikum Kassel
city: Mainz
country: Germany
facility: Neurochirurgische Klinik, Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Neurochirurgische Klinik, Universitätsklinikum Mannheim
city: Munich
country: Germany
facility: Dep. of Neurosurgery, Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Klinik für Allgemeine Neurologie, Universitätsklinikum Münster
city: Würzburg
country: Germany
facility: Klinik für Neurochirurgie, Universitätsklinikum Würzburg
city: Amsterdam
country: Netherlands
facility: Academic Medical Center Amsterdam, Department of Neurology
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht, Department of Neurology, Department of Neurosurgery
city: Barcelona
country: Spain
facility: Servicio de Neurocirurgía Bellvitge Hospital
city: Madrid
country: Spain
facility: Servicio de Neurología, Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Servicios de Neurología, Neurocirugía y Cuidados Intensivos del Hospital Virgen del Rocío
city: Bern
country: Switzerland
facility: Dep. of Neurology / Dep. of Neurosurgery, Bern University Hospital
city: Geneva
country: Switzerland
facility: Dep. of Clinical Neuroscience, Service of Neurosurgery
city: Lugano
country: Switzerland
facility: Dep. Neurosurgery, Ospedale Regionale di Lugano
city: Zürich
country: Switzerland
facility: Dep. of Neurosurgery, University Hospital Zürich
Study officials:
affiliation: Dep. of Neurology, Inselspital Bern
name: Urs Fischer, Prof. Dr. med.
role: STUDY_DIRECTOR
affiliation: Dep. of Neurosurgery, Inselspital Bern
name: Jürgen Beck, Prof. Dr. med.
role: STUDY_CHAIR
References: