. 2018 Dec 4;19(1):670.

doi: 10.1186/s13063-018-3050-4.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial

Angelos G Kolias^{1

2}, Ellie Edlmann^{3

4}, Eric P Thelin^{5

6}, Diederik Bulters⁷, Patrick Holton⁷, Nigel Suttner⁸, Kevin Owusu-Agyemang⁸, Yahia Z Al-Tamimi⁹, Daniel Gatt⁹, Simon Thomson¹⁰, Ian A Anderson¹⁰, Oliver Richards¹⁰, Peter Whitfield¹¹, Monica Gherle¹¹, Karen Caldwell¹², Carol Davis-Wilkie¹³, Silvia Tarantino¹², Garry Barton¹⁴, Hani J Marcus¹⁵, Aswin Chari¹⁶, Paul Brennan¹⁷, Antonio Belli¹⁸, Simon Bond^{13

19}, Carole Turner^{5

12}, Lynne Whitehead²⁰, Ian Wilkinson¹³, Peter J Hutchinson^{21

22}; British Neurosurgical Trainee Research Collaborative (BNTRC) and Dex-CSDH Trial Collaborators

Collaborators, Affiliations

Collaborators

British Neurosurgical Trainee Research Collaborative (BNTRC) and Dex-CSDH Trial Collaborators:
Khaled Badran, Ian Coulter, Mathew J Gallagher, Florence R A Hogg, Catherine Pringle, Adam Razak, Hamzah Soleiman, Rory Piper, Emma Toman, Marian Vintu, Adam Wahba, Anthony Wiggins, Kamal Makram Yakoub, Malik Zaben, Ardalan Zolnouria, Peter Bodkin, Emanuel Cirstea, Giles Critchley, Charlotte Eglinton, Louise Finlay, Daniela Georgieva, Nihal Gurusinghe, Nikolaos Haliasos, Damian Holliman, Kismet Hossain-Ibrahim, Masood Hussain, Jothy Kandasamy, Mary Kambafwile, Phillip Kane, Dipankar Nandi, Ravindra Nannapaneni, Laura Ortiz-Ruiz de Gordoa, Marios C Papadopoulos, Dimitris Paraskevopoulos, Jash Patel, Manjunath Prasad, Nikolaos Tzerakis, Carol Brayne, Andrew Gardner, Andrew King, Kate Massey, Thais Minett, Patrick Mitchell, Phyo Myint, Elizabeth Warburton, Anthony Bell, Allison Hirst, Laurence Watkins, Peter McCabe, Martin Smith, Joan Grieve, Jonathan Cook

Affiliations

¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. ak721@cam.ac.uk.
² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. ak721@cam.ac.uk.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. ee291@cam.ac.uk.
⁴ Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. ee291@cam.ac.uk.
⁵ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁷ Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Tremona Rd, Southampton, Hampshire, SO16 6YD, UK.
⁸ Institute of Neurosciences, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, UK.
⁹ Department of Neurosurgery, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.
¹⁰ Department of Neurosurgery, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK.
¹¹ Southwest Neurosurgical Centre, Plymouth University Hospitals NHS trust, Plymouth, PL6 8DH, UK.
¹² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK.
¹³ Cambridge Clinical Trials Unit (CCTU), Coton House, Level 6, Cambridge Biomedical Campus, Box 401, Cambridge, CB2 0QQ, UK.
¹⁴ Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.
¹⁵ Imperial College Healthcare NHS Trust, South Kensington Campus, London, SW7 2AZ, UK.
¹⁶ Royal London Hospital, Barts Health NHS trust, Whitechapel Road, London, E1 1BB, UK.
¹⁷ Department of Clinical Neurosciences, University of Edinburgh, Western General Hospitals NHS Trust, Crewe Road, Edinburgh, EH4 2XU, UK.
¹⁸ NIHR Surgical Reconstruction and Microbiology Research Centre & University Hospitals Birmingham NHS Foundation Trust, School of Clinical and Experimental Medicine, University of Birmingham, Institute of Biomedical Research (West), Room WX 2.61, Edgbaston, Birmingham, B15 2TT, UK.
¹⁹ MRC Biostatistics Unit, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.
²⁰ Clinical Trials Pharmacy, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
²¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. pjah2@cam.ac.uk.
²² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. pjah2@cam.ac.uk.

PMID: 30514400
PMCID: PMC6280536
DOI: 10.1186/s13063-018-3050-4

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial

Angelos G Kolias et al. Trials. 2018.

. 2018 Dec 4;19(1):670.

doi: 10.1186/s13063-018-3050-4.

Authors

Collaborators

British Neurosurgical Trainee Research Collaborative (BNTRC) and Dex-CSDH Trial Collaborators:
Khaled Badran, Ian Coulter, Mathew J Gallagher, Florence R A Hogg, Catherine Pringle, Adam Razak, Hamzah Soleiman, Rory Piper, Emma Toman, Marian Vintu, Adam Wahba, Anthony Wiggins, Kamal Makram Yakoub, Malik Zaben, Ardalan Zolnouria, Peter Bodkin, Emanuel Cirstea, Giles Critchley, Charlotte Eglinton, Louise Finlay, Daniela Georgieva, Nihal Gurusinghe, Nikolaos Haliasos, Damian Holliman, Kismet Hossain-Ibrahim, Masood Hussain, Jothy Kandasamy, Mary Kambafwile, Phillip Kane, Dipankar Nandi, Ravindra Nannapaneni, Laura Ortiz-Ruiz de Gordoa, Marios C Papadopoulos, Dimitris Paraskevopoulos, Jash Patel, Manjunath Prasad, Nikolaos Tzerakis, Carol Brayne, Andrew Gardner, Andrew King, Kate Massey, Thais Minett, Patrick Mitchell, Phyo Myint, Elizabeth Warburton, Anthony Bell, Allison Hirst, Laurence Watkins, Peter McCabe, Martin Smith, Joan Grieve, Jonathan Cook

Affiliations

¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. ak721@cam.ac.uk.
² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. ak721@cam.ac.uk.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. ee291@cam.ac.uk.
⁴ Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. ee291@cam.ac.uk.
⁵ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁷ Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Tremona Rd, Southampton, Hampshire, SO16 6YD, UK.
⁸ Institute of Neurosciences, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, UK.
⁹ Department of Neurosurgery, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.
¹⁰ Department of Neurosurgery, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK.
¹¹ Southwest Neurosurgical Centre, Plymouth University Hospitals NHS trust, Plymouth, PL6 8DH, UK.
¹² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK.
¹³ Cambridge Clinical Trials Unit (CCTU), Coton House, Level 6, Cambridge Biomedical Campus, Box 401, Cambridge, CB2 0QQ, UK.
¹⁴ Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.
¹⁵ Imperial College Healthcare NHS Trust, South Kensington Campus, London, SW7 2AZ, UK.
¹⁶ Royal London Hospital, Barts Health NHS trust, Whitechapel Road, London, E1 1BB, UK.
¹⁷ Department of Clinical Neurosciences, University of Edinburgh, Western General Hospitals NHS Trust, Crewe Road, Edinburgh, EH4 2XU, UK.
¹⁸ NIHR Surgical Reconstruction and Microbiology Research Centre & University Hospitals Birmingham NHS Foundation Trust, School of Clinical and Experimental Medicine, University of Birmingham, Institute of Biomedical Research (West), Room WX 2.61, Edgbaston, Birmingham, B15 2TT, UK.
¹⁹ MRC Biostatistics Unit, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.
²⁰ Clinical Trials Pharmacy, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
²¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. pjah2@cam.ac.uk.
²² Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge, CB2 0QQ, UK. pjah2@cam.ac.uk.

PMID: 30514400
PMCID: PMC6280536
DOI: 10.1186/s13063-018-3050-4

Erratum in

Correction to: Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.
Kolias AG, Edlmann E, Thelin EP, Bulters D, Holton P, Suttner N, Owusu-Agyemang K, Al-Tamimi YZ, Gatt D, Thomson S, Anderson IA, Richards O, Whitfield P, Gherle M, Caldwell K, Davis-Wilkie C, Tarantino S, Barton G, Marcus HJ, Chari A, Brennan P, Belli A, Bond S, Turner C, Whitehead L, Wilkinson I, Hutchinson PJ; British Neurosurgical Trainee Research Collaborative (BNTRC) and Dex-CSDH Trial Collaborators. Kolias AG, et al. Trials. 2019 Mar 18;20(1):175. doi: 10.1186/s13063-019-3283-x. Trials. 2019. PMID: 30885268 Free PMC article.

Abstract

Background: Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions.

Methods: Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis.

Discussion: This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition.

Trial registration: ISRCTN, ISRCTN80782810 . Registered on 7 November 2014. EudraCT, 2014-004948-35 . Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.

Keywords: Chronic subdural haematoma; Dexamethasone; Neurology; Neurosurgery; Randomised control trial.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The Dex-CSDH trial protocol version 3, 27 Apr 2017, informed consent forms and all other relevant trial documents have been approved by North West-Haydock Research and Ethics Committee (REC), reference 15/NW/0171.

All correspondence with the REC will be retained in the Trial Master File and Investigator Site File. Annual reports will be submitted to the REC in accordance with national requirements. The trial will be performed in accordance with the SPIRIT guidelines and the letter of the declaration of Helsinki, the conditions and principles of GCP, the protocol and applicable local regulatory requirements and laws.

Protocol violations, deviations, non-compliances or breaches are departures from the approved protocol and must be adequately documented and reported to the Chief Investigator and Sponsor immediately. Any potential/suspected serious breaches of GCP must be reported immediately to the sponsor without any delay.

Consent for publication

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The sponsors and funders reviewed the study design, management and analysis plan before approving the trial. Ownership of the data arising from this trial resides with the trial management group, who will decide on publication and authorship. On completion of the trial, the data will be analysed and tabulated and a final trial report will be prepared.

TMG members: Peter J Hutchinson (Chief Investigator), Ellie Edlmann (Trial fellow and trainee Lead Investigator), Eric Thelin (Trial Fellow), Angelos G Kolias (Co-chief Investigator), Karen Caldwell (Research nurse), Silvia Tarantino (Research nurse), Carol Davis-Wilkie (trial coordinator), Carol Turner (Research manager), Simon Bond (Statistician), Beatrice Pantaleo (Data manager).

Trial sponsors:

The Chancellor, Masters and Scholars of the University of Cambridge, The Old Schools, Trinity Lane, Cambridge CB2 1TN; and
Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ.

Cambridge University Hospitals NHS Foundation Trust, as a member of the NHS Clinical Negligence Scheme for Trusts, will accept full financial liability for harm caused to patients in the clinical trial caused through the negligence of its employees and honorary contract holders. There are no specific arrangements for compensation should a patient be harmed through participation in the trial, but no-one has acted negligently. The University of Cambridge will arrange insurance for negligent harm caused as a result of protocol design and for non-negligent harm arising through participation in the clinical trial.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Schedule of assessments. * = only collected in patients recruited to sub-study in coordinating centre. Ax within 72 h of admission to NSU, AE adverse event, D day, D/C discharge (or death if sooner), EQ-5D European Quality of life-5 dimensions, IMP investigational medicinal product, I-O intraoperative, mon months, mRS modified Rankin Scale

See this image and copyright information in PMC

References

1. Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, et al. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009;374(9695):1067–1073. doi: 10.1016/S0140-6736(09)61115-6. - DOI - PubMed
1. Berhauser Pont LM, Dammers R, Schouten JW, Lingsma HF, Dirven CM. Clinical factors associated with outcome in chronic subdural hematoma: a retrospective cohort study of patients on preoperative corticosteroid therapy. Neurosurgery. 2012;70(4):873–880. doi: 10.1227/NEU.0b013e31823672ad. - DOI - PubMed
1. Delgado-López PD, Martín-Velasco V, Castilla-Díez JM, Rodríguez-Salazar A, Galacho-Harriero AM, Fernández-Arconada O. Dexamethasone treatment in chronic subdural haematoma. Neurocirugia (Astur) 2009;20(4):346–359. doi: 10.1016/S1130-1473(09)70154-X. - DOI - PubMed
1. Sun TF, Boet R, Poon WS. Non-surgical primary treatment of chronic subdural haematoma: Preliminary results of using dexamethasone. Br J Neurosurg. 2005;19(4):327–333. doi: 10.1080/02688690500305332. - DOI - PubMed
1. Berghauser Pont LM, Dirven CM, Dippel DW, Verweij BH, Dammers R. The role of corticosteroids in the management of chronic subdural hematoma: a systematic review. Eur J Neurol. 2012;19(11):1397–1403. doi: 10.1111/j.1468-1331.2012.03768.x. - DOI - PubMed

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Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial

Collaborators

Affiliations

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial

Authors

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

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