Decompressive Hemicraniectomy in Intracerebral Hemorrhage

NCT ID: NCT02258919

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2024-05-23

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.

Conditions

Cerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Decompressive craniectomy and best medical treatment

Decompressive craniectomy and best medical treatment

Group Type: EXPERIMENTAL

Decompressive craniectomy (DC) and best medical treatment

Intervention Type: PROCEDURE

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

Group Type: ACTIVE_COMPARATOR

Best medical treatment

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Urs Fischer, Prof. Dr. med.

Role: STUDY_DIRECTOR

Dep. of Neurology, Inselspital Bern

Jürgen Beck, Prof. Dr. med.

Role: STUDY_CHAIR

Dep. of Neurosurgery, Inselspital Bern

Locations

Universitätsklinik für Neurochirurgie, Kepler Universitätsklinikum Linz

Linz, , Austria

UZ Leuven

Leuven, , Belgium

Department of Neurology, Helsinki University Central Hospital

Helsinki, , Finland

Centre Hospitalier Universitaire de Caen

Caen, , France

Fondation Adolphe de Rothschild

Paris, , France

Klinik für Neurochirurgie, Universitätsklinikum Schleswig Holstein

Lübeck, Schleswig-Holstein, Germany

Klinik für Neurochirugie, Helios Klinikum Erfurt

Erfurt, Thuringia, 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

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 im Breisgau, , Germany

Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg UKGM

Giessen, , Germany

Klinik für Neurochirurgie, Universitätsmedizin Göttingen

Göttingen, , Germany

Klinik für Neurochirurgie, Klinikum Kassel

Kassel, , 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, , Germany

Academic Medical Center Amsterdam, Department of Neurology

Amsterdam, , Netherlands

University Medical Center Utrecht, Department of Neurology, Department of Neurosurgery

Utrecht, , Netherlands

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

Seville, , Spain

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

Zurich, , Switzerland

Countries

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

References

Polymeris AA, Lang MF, Hakim A, Butikofer L, Fung C, Beyeler S, Z'Graggen W, Strbian D, Vajkoczy P, Schubert GA, Gruber A, Mielke D, Roelz R, Siepen B, Seiffge DJ, Selim MH, Raabe A, Beck J, Fischer U; SWITCH study investigators. Effect of Decompressive Craniectomy According to Location of Deep Intracerebral Hemorrhage: A SWITCH Trial Analysis. Stroke. 2025 Oct 17. doi: 10.1161/STROKEAHA.125.052460. Online ahead of print.

Reference Type: DERIVED

PMID: 41104458 (View on PubMed)

Beck J, Fung C, Strbian D, Butikofer L, Z'Graggen WJ, Lang MF, Beyeler S, Gralla J, Ringel F, Schaller K, Plesnila N, Arnold M, Hacke W, Juni P, Mendelow AD, Stapf C, Al-Shahi Salman R, Bressan J, Lerch S, Hakim A, Martinez-Majander N, Piippo-Karjalainen A, Vajkoczy P, Wolf S, Schubert GA, Hollig A, Veldeman M, Roelz R, Gruber A, Rauch P, Mielke D, Rohde V, Kerz T, Uhl E, Thanasi E, Huttner HB, Kallmunzer B, Jaap Kappelle L, Deinsberger W, Roth C, Lemmens R, Leppert J, Sanmillan JL, Coutinho JM, Hackenberg KAM, Reimann G, Mazighi M, Bassetti CLA, Mattle HP, Raabe A, Fischer U; SWITCH study investigators. Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial. Lancet. 2024 Jun 1;403(10442):2395-2404. doi: 10.1016/S0140-6736(24)00702-5. Epub 2024 May 15.

Reference Type: DERIVED

PMID: 38761811 (View on PubMed)

Fischer U, Fung C, Beyeler S, Butikofer L, Z'Graggen W, Ringel F, Gralla J, Schaller K, Plesnila N, Strbian D, Arnold M, Hacke W, Juni P, Mendelow AD, Stapf C, Al-Shahi Salman R, Bressan J, Lerch S, Bassetti CLA, Mattle HP, Raabe A, Beck J. Swiss trial of decompressive craniectomy versus best medical treatment of spontaneous supratentorial intracerebral haemorrhage (SWITCH): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial. Eur Stroke J. 2024 Sep;9(3):781-788. doi: 10.1177/23969873241231047. Epub 2024 Feb 12.

Reference Type: DERIVED

PMID: 38347736 (View on PubMed)

Related Links

http://www.switch-trial.ch

Website of the trial

Other Identifiers

32003B_150009

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

163/14

Identifier Type: -

Identifier Source: org_study_id