Decompressive Hemicraniectomy in Intracerebral Hemorrhage

Cerebral Hemorrhage Clinical Trial

— SWITCH  

Official title:

Swiss Trial of Decompressive Craniectomy Versus Best Medical Treatment of Spontaneous Supratentorial Intracerebral Hemorrhage (SWITCH): a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02258919
• Other study ID #: 163/14
• Secondary ID: 32003B_150009
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 2014
• Est. completion date: May 23, 2024

Study information

• Verified date: June 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 201
• Est. completion date: May 23, 2024
• Est. primary completion date: October 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage

Intervention

Procedure:
• Decompressive craniectomy (DC) and best medical treatment
Decompressive craniectomy: All patients in the treatment group will receive DC of at least 12 cm according to institutional guidelines and a published surgical protocol. Best medical treatment: Best medical treatment is based on American Heart Association/American Stroke Association (AHA/ASA) and European Stroke Organisation (ESO) as published in the current protocol from 2010 and 2014 respectively.
• Best medical treatment
Best medical treatment is based on American Heart Association/American Stroke Association (AHA/ASA) and European Stroke Organisation (ESO) as published in the current protocol from 2010 and 2014 respectively.

Locations

Country	Name	City	State
Austria	Universitätsklinik für Neurochirurgie, Kepler Universitätsklinikum Linz	Linz
Belgium	UZ Leuven	Leuven
Finland	Department of Neurology, Helsinki University Central Hospital	Helsinki
France	Centre Hospitalier Universitaire de Caen	Caen
France	Fondation Adolphe de Rothschild	Paris
Germany	Klinik für Neurochirurgie Uniklinik RWTH Aachen	Aachen
Germany	Department of Neurosurgery, Charité - Universitätsmedizin Berlin	Berlin
Germany	Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Bonn	Bonn
Germany	Klinik für Neurochirurgie, Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Klinik für Neurochirugie, Helios Klinikum Erfurt	Erfurt	Thüringen
Germany	Neurologische Klinik, Universitätsklinikum Erlangen	Erlangen
Germany	Klinik für Neurochirurgie, Universitätsklinikum Essen (AöR)	Essen
Germany	Zentrum der Neurologie und Neurochirurgie, Universitätsklinikum Frankfurt	Frankfurt
Germany	Klinik für Neurochirurgie, Universitätsklinikum Freiburg	Freiburg
Germany	Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg UKGM	Gießen
Germany	Klinik für Neurochirurgie, Universitätsmedizin Göttingen	Göttingen
Germany	Klinik für Neurochirurgie, Klinikum Kassel	Kassel
Germany	Klinik für Neurochirurgie, Universitätsklinikum Schleswig Holstein	Lübeck	Schleswig Holstein
Germany	Neurochirurgische Klinik, Universitätsmedizin Mainz	Mainz
Germany	Neurochirurgische Klinik, Universitätsklinikum Mannheim	Mannheim
Germany	Dep. of Neurosurgery, Klinikum rechts der Isar der Technischen Universität München	Munich
Germany	Klinik für Allgemeine Neurologie, Universitätsklinikum Münster	Münster
Germany	Klinik für Neurochirurgie, Universitätsklinikum Würzburg	Würzburg
Netherlands	Academic Medical Center Amsterdam, Department of Neurology	Amsterdam
Netherlands	University Medical Center Utrecht, Department of Neurology, Department of Neurosurgery	Utrecht
Spain	Servicio de Neurocirurgía Bellvitge Hospital	Barcelona
Spain	Servicio de Neurología, Hospital Universitario La Paz	Madrid
Spain	Servicios de Neurología, Neurocirugía y Cuidados Intensivos del Hospital Virgen del Rocío	Sevilla
Switzerland	Dep. of Neurology / Dep. of Neurosurgery, Bern University Hospital	Bern
Switzerland	Dep. of Clinical Neuroscience, Service of Neurosurgery	Geneva
Switzerland	Dep. Neurosurgery, Ospedale Regionale di Lugano	Lugano
Switzerland	Dep. of Neurosurgery, University Hospital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Countries where clinical trial is conducted

Austria,  Belgium,  Finland,  France,  Germany,  Netherlands,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Score in modified Rankin Scale (mRS)	Assessed by telephone interview	6 months
Secondary	Mortality		7 days, 30 days, 180 days, 12 months
Secondary	mRS score of 0-3 versus 4-6		30 days, 180 days, 12 months
Secondary	Categorical shift in mRS score		180 days, 12 months
Secondary	Quality of life		180 days, 12 months
Secondary	Death and intracranial hemorrhage		intraoperative

External Links

•   Website of the trial