Decompressive Hemicraniectomy in Intracerebral Hemorrhage (SWITCH)

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Hemorrhage
• Intervention / Treatment: Procedure: Decompressive craniectomy (DC) and best medical treatment; Procedure: Best medical treatment

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.

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4020
    • Universitätsklinik für Neurochirurgie, Kepler Universitätsklinikum Linz
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Finland
  • Helsinki, Finland, 00290
    • Department of Neurology, Helsinki University Central Hospital
• France
  • Caen, France, 14033
    • Centre Hospitalier Universitaire de Caen
  • Paris, France, 75019
    • Fondation Adolphe de Rothschild
• Germany
  • Aachen, Germany, 52074
    • Klinik für Neurochirurgie Uniklinik RWTH Aachen
  • Berlin, Germany, 13353
    • Department of Neurosurgery, Charité - Universitätsmedizin Berlin
  • Bonn, Germany, 53127
    • Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Bonn
  • Düsseldorf, Germany, 40225
    • Klinik für Neurochirurgie, Universitätsklinikum Düsseldorf
  • Erlangen, Germany, 91054
    • Neurologische Klinik, Universitätsklinikum Erlangen
  • Essen, Germany, 45147
    • Klinik für Neurochirurgie, Universitätsklinikum Essen (AöR)
  • Frankfurt, Germany, 60590
    • Zentrum der Neurologie und Neurochirurgie, Universitätsklinikum Frankfurt
  • Freiburg, Germany, 79106
    • Klinik für Neurochirurgie, Universitätsklinikum Freiburg
  • Gießen, Germany, 35392
    • Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg UKGM
  • Göttingen, Germany, 37075
    • Klinik für Neurochirurgie, Universitätsmedizin Göttingen
  • Kassel, Germany, 34125
    • Klinik für Neurochirurgie, Klinikum Kassel
  • Mainz, Germany, 55116
    • Neurochirurgische Klinik, Universitätsmedizin Mainz
  • Mannheim, Germany, 68167
    • Neurochirurgische Klinik, Universitätsklinikum Mannheim
  • Munich, Germany, 81675
    • Dep. of Neurosurgery, Klinikum rechts der Isar der Technischen Universität München
  • Münster, Germany, 48149
    • Klinik für Allgemeine Neurologie, Universitätsklinikum Münster
  • Würzburg, Germany, 97080
    • Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Schleswig Holstein
    • Lübeck, Schleswig Holstein, Germany, 23562
      • Klinik für Neurochirurgie, Universitätsklinikum Schleswig Holstein
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
      • Klinik für Neurochirugie, Helios Klinikum Erfurt
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Academic Medical Center Amsterdam, Department of Neurology
  • Utrecht, Netherlands, 3584
    • University Medical Center Utrecht, Department of Neurology, Department of Neurosurgery
• Spain
  • Barcelona, Spain, 08907
    • Servicio de Neurocirurgía Bellvitge Hospital
  • Madrid, Spain, 28046
    • Servicio de Neurología, Hospital Universitario La Paz
  • Sevilla, Spain, 41013
    • Servicios de Neurología, Neurocirugía y Cuidados Intensivos del Hospital Virgen del Rocío
• Switzerland
  • Bern, Switzerland, 3010
    • Dep. of Neurology / Dep. of Neurosurgery, Bern University Hospital
  • Geneva, Switzerland, 1211
    • Dep. of Clinical Neuroscience, Service of Neurosurgery
  • Lugano, Switzerland, 6903
    • Dep. Neurosurgery, Ospedale Regionale di Lugano
  • Zürich, Switzerland, 8091
    • Dep. of Neurosurgery, University Hospital Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decompressive craniectomy and best medical treatment	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.
Active Comparator: Best medical treatment	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score in modified Rankin Scale (mRS)	Assessed by telephone interview	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	7 days, 30 days, 180 days, 12 months
mRS score of 0-3 versus 4-6	30 days, 180 days, 12 months
Categorical shift in mRS score	180 days, 12 months
Quality of life	180 days, 12 months
Death and intracranial hemorrhage	intraoperative

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Study Director: Urs Fischer, Prof. Dr. med., Dep. of Neurology, Inselspital Bern; Study Chair: Jürgen Beck, Prof. Dr. med., Dep. of Neurosurgery, Inselspital Bern

Publications and helpful links

Helpful Links

• Website of the trial

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): October 15, 2023
• Study Completion (Actual): May 23, 2024

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimated): October 8, 2014

Study Record Updates

• Last Update Posted (Actual): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Acute stroke; Intracerebral hemorrhage; Decompressive craniectomy
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: 163/14; 32003B_150009 (Other Grant/Funding Number: SNF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No