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Decompressive Surgery Plus Hypothermia for Space occupying Stroke (Depth-SOS)

Organizational Data

DRKS-ID:
DRKS00000623
Recruitment Status:
Recruiting complete, study complete
Date of registration in DRKS:
2011-03-21
Last update in DRKS:
2021-03-05
Registration type:
Prospective

Acronym/abbreviation of the study

DEPTH-SOS DEcompressive Surgery Plus Hypothermia in Space Occupying Stroke

URL of the study

No Entry

Brief summary in lay language

Patients with space-occupying hemispheric infarctions of the middle cerebral artery have a poor prognosis. Despite maximal conservative and intensive care treatment only 20% of patients survive. Hemicraniectomy has been shown to reduce mortality from 70% to 20% in randomized controlled trials. Furthermore, the proportion of severely disabled patients is low (4%-5%) and does not differ compared to conservative treatment. Induced hypothermia is frequently used in critically ill patients for neuroprotection and has been shown to be effective in preventing hypoxic brain damage after cardiac arrest in large randomized controlled trials. There are several pilot studies also for ischemic stroke. However, there are no larger prospective randomized trials investigating induced hypothermia in malignant cerebral infarction. The aim of this study is to determine the safety and feasibility of combined hemicraniectomy and mild hypothermia (33-34 °C) in patients with space-occupying hemispheric infarctions versus hemicraniectomy alone.

Brief summary in scientific language

Subtotal or complete infarctions of the middle cerebral artery (MCA) territory, occasionally with additional infarctions of the anterior cerebral artery (ACA) or the posterior cerebral artery (PCA) or both, are found in 1% to 10% of patients with ischemic supratentorial infarcts. These infarctions are commonly associated with serious brain swelling. Mass effect leads to the destruction of formerly healthy brain tissue, and, in severe cases, to extensive brain tissue shifts resulting in transforaminal, transtentorial, or uncal herniation and brain death in most cases. Because conservative treatment options usually fail, early decompressive hemicraniectomy has been used for several years as an alternative therapy. Meanwhile the benefit of hemicraniectomy has been demonstrated in randomized controlled trials in patients up to 60 years of age. Induced hypothermia is defined as lowering of the physiological body core temperature which can be achieved by external or intravascular cooling devices. Hypothermia excerts its neuroprotective effects through various mechanisms including changes of the cerebral metabolism, stabilizartion of the blood-brain-barrier and inhibition of excytotoxic neuronal damage. These neuroprotective effects have been shown in randomized trials in patients with global hypoxia who were treated with induced hypothermia after cardiac arrest. Furthermore, clinical studies have shown that elevated core body temperature is an independent predictor for mortality and bad functional outcome in acute stroke. Induced hypothermia in combination with decompressive surgery is used in some centers for the treatment of patients with malignant MCA infarctions on an indicidual basis. This study aims to investigate the safety and feasibility of mild induced hypothermia combisned with hemicraniectomy . Amendment: The authors decided to use a more conservative sample size calculation after the first safety analysis including the first 10 patients. Instead of a maximum of 71 patients included, an interim analysis will be conducted after patient 50. The decision to continue the trial will depend on the results of the interim analysis. Furthermore, the primary endpoint was defined more clearly as mortality on day 14. Mortality at discharge was cancelled. (Re-No 4349, 14.12.2011)

Health condition or problem studied

ICD10:
I63 - Cerebral infarction
Healthy volunteers:
No Entry

Interventions, Observational Groups

Arm 1:
decompressive hemicraniectomy
Arm 2:
decompressive hemicraniectomy plus induced mild hypothermia (32-34°C)

Endpoints

Primary outcome:
The primary endpoint is mortality at discharge (day 14).
Secondary outcome:
1. Time from symptom onset to death or time from symptom onset to discharge 2. Disability according to the modified Rankin Scale after 6 months 3. Disability (Barthel index) after 6 months 4. Neurological status (NIHSS) after 6 months 5. Complications related to surgery 6. Complications realted to hypothermia 7. Rate of pneumonia 8. Sepsis 9. Use of katecholamines 10. Duration of ventilation 11. Duration of hypothermia 12. Time to target temperature 13. Rate of major bleedings 14. Rate of deep venous thromboses 15. Rate of pulmonary embolism

Study Design

Purpose:
Other
Allocation:
Randomized controlled study
Control:
  • Active control (effective treatment of control group)
Phase:
N/A
Study type:
Interventional
Mechanism of allocation concealment:
No Entry
Blinding:
No
Assignment:
Parallel
Sequence generation:
No Entry
Who is blinded:
No Entry

Recruitment

Recruitment Status:
Recruiting complete, study complete
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Multicenter study
Recruitment location(s):
  • University medical center Klinik für Neurologie Dresden
  • University medical center Neurologische Klinik Tübingen
  • University medical center Klinik für Neurologie Berlin
  • University medical center Neurologische Klinik Erlangen
  • University medical center Klinik für Neurologie Heidelberg
  • University medical center Klinik für Neurologie Leipzig

Recruitment period and number of participants

Planned study start date:
2011-04-01
Actual study start date:
2011-08-10
Planned study completion date:
No Entry
Actual Study Completion Date:
2016-09-08
Target Sample Size:
50
Final Sample Size:
50

Inclusion Criteria

Sex:
All
Minimum Age:
18 Years
Maximum Age:
60 Years
Additional Inclusion Criteria:
1. Clinical signs of infarction in the territory of the MCA 2. Score on the National Institutes of Health stroke scale (NIHSS) >14 (in non-dominant hemispheric infarctions) or >19 (in dominant hemispheric infarctions). * 3. Score in the level of consciousness (item 1a of the NIHSS) of 1 or more. * 4. Definite infarction on CT or MRI of at least 2/3 of the MCA territory, with involvement of the basal ganglia, with or without additional infarction of the territory of the anterior or posterior cerebral artery on the same side, or infarct volume >145 cm3 as shown on diffusion-weighted MRI. Imaging related inclusion and exclusion criteria may be obtained at initial presentation or at follow-up imaging before randomization and within 48h from symptom onset to operation. 5. Decision for hemicraniectomie has been made by the treating physician(s). 6. Hemicraniectomy within 48h after symptom onset. 7. Induced Hypothermia within 12h after hemicraniectomy 8. Informed consent by either the patient, the legal representative, a judge, or by an independet physician. 9. *Inclusion criteria 2 and 3 do not apply for in intubated, ventilated, sedated and/or relaxated patients and are therefore not considered in these patients.

Exclusion Criteria

1. age ≥61 years. 2. prestroke mRS ≥2 or Barthel-index < 95. 3. concomittant additional brain damage in (e.g. traumatic brain injury, contralateral ischaemia) that could confound the treatmnt effect on outcome. 4. bilateral fixed dilated pupils. 5. GCS <6. 6. space-occupying haemorrhagic. transformation of the infarct (≥parenchymal haemorrhage grade 2). 7. known coagulopathy or systemic bleeding disorder. 8. life expectancy <3 years. 9. contraindication for hypothermia. 10. known contraindication haematological diseases (kryoglobulinemia, cold agglutination, sikcle cell anemia). 11. known vasopastic vascular disease (M. Raynaud, endangiitis obliterans). 12. pregnancy. 13. advanced malignancy with poor prognosis. 14. severe inflammatory response syndrome or sepsis. 15. local conditions which make catheters placement impossible (maceration or severe infection of the skin, arterial aneurysm on both femoral arteries). 16. Known indication for hypothermia (e.g. cardiopulmonal resuscitation) 17. Participation in other interventional trial (participation in observational trials is possible)

Addresses

Primary Sponsor

Ostalb-Klinikum Aalen
PD Dr. med. MSc Eric Jüttler
Am Kälbesrain 1
73430 Aalen
Germany
Telephone:
0049-7361-55-1701
Fax:
0049-7361-55-1703
Contact per E-Mail
URL:
No Entry
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Ostalb-Klinikum Aalen
PD Dr. med. MSc. Eric Jüttler
Am Kälbesrain 1
73420 Aalen
Germany
Telephone:
0049-7361-55-1701
Fax:
0049-7361-55-1703
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

Universitäts- und Rehabilitationskliniken Ulm, RKU, Klinik für Neurologie
Dr. med. M.Sc. Hermann Neugebauer
Oberer Eselsberg 45
89081 Ulm
Germany
Telephone:
0049-731-177-5227
Fax:
0049-731-177-1280
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Institutional budget, no external funding (budget of sponsor/PI)

Centrum für Schlaganfallforschung Berlin (CSB) Charite - Universitätsmedizin Berlin Campus Virchow-Klinikum
Augustenburger Platz 1
13353 Berlin
Germany
Telephone:
030-450-560-615
Fax:
030-450-560-957
Contact per E-Mail
URL:
http://www.charite.de

Ethics Committee

Address Ethics Committee

Ethik-Kommission der Medizinischen Fakultät der Universität Erlangen-Nürnberg
Krankenhausstr. 12
91054 Erlangen
Germany
Telephone:
+40-9131-8522270
Fax:
+49-9131-8526021
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Date of ethics committee application:
2010-11-09
Ethics committee number:
4349
Vote of the Ethics Committee:
Approved
Date of the vote:
2011-02-24

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
No Entry
UTN (Universal Trial Number):
U1111-1119-9481
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
Yes
IPD Sharing Plan:
Individual patient data reported as results after deidentification as well as the study protocol, 9 month to 36 months after publication, after propsosal was reviewed by an independent committee, for individual patient data meta-analyses.

Study protocol and other study documents

Study protocols:
No Entry
Study abstract:
No Entry
Other study documents:
No Entry
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
Neugebauer H, Schneider H, Bösel J, Hobohm C, Poli S, Kollmar R, Sobesky J, Wolf S, Bauer M, Tittel S, Beyersmann J, Woitzik J, Heuschmann PU, Jüttler E. Outcomes of Hypothermia in Addition to Decompressive Hemicraniectomy in Treatment of Malignant Middle Cerebral Artery Stroke: A Randomized Clinical Trial. JAMA Neurol. 2019 May 1;76(5):571-579. doi: 10.1001/jamaneurol.2018.4822. Erratum in: JAMA Neurol. 2019 Feb 25;: PMID: 30801622; PMCID: PMC6515575.
https://doi.org/10.1001/jamaneurol.2018.4822
Date of first publication of study results:
No Entry
DRKS entry published for the first time with results:
No Entry

Basic reporting

Basic Reporting / Results tables:
No Entry
Brief summary of results:
No Entry