BMJ Open (Aug 2023)
Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma – protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial
- ,
- Khalid Hamandi,
- Julie Woodfield,
- Smriti Agarwal,
- Richard Edwards,
- John Williamson,
- Ravindran Visagan,
- Rustam Al-Shahi Salman,
- Howard Brydon,
- Diederik Bulters,
- Dawn Hennigan,
- Paul Leach,
- Conor Mallucci,
- Nitin Mukerji,
- Marios Papadopoulos,
- Nicholas Ross,
- Martin Tisdall,
- Carole Turner,
- Shungu Ushewokunze,
- Raghu Vindlacheruvu,
- Paul Brennan,
- Phil White,
- Sophie Hunter,
- Karen Coy,
- Julia Wade,
- James Stewart,
- Tom Hughes,
- Laura Forsyth,
- Kirsty Harkness,
- David White,
- Rupal Shah,
- Sanjay Bhate,
- Neil Kitchen,
- Peter J Hutchinson,
- Emanuel Cirstea,
- Ramesh Nair,
- Rebecca Hall,
- Varduhi Cahill,
- Tom Hayton,
- Silvia Tarantino,
- Christin Eltze,
- Jack Lee,
- Arlo Whitehouse,
- Daniel Walsh,
- Jacqueline Stephen,
- Nicola Phillips,
- Steff Lewis,
- Susan Davies,
- Mathew Guilfoyle,
- Peter S Hall,
- Andrew Stoddart,
- Francesca Colombo,
- Emma Richards,
- Greg James,
- Sarah Illingworth,
- William B Lo,
- Andrew Bacon,
- Vijeya Ganesan,
- Sabina Patel,
- Aileen R Neilson,
- Felicia Jennings,
- Saba Raza-Knight,
- Andrew Brodbelt,
- Aswin Chari,
- Hasan Asif,
- Ian Kamaly-Asl,
- Milan Makwana,
- Zubair Tahir,
- Allan MacRaild,
- Rustam Al-Shahi Salman,
- Grace Vassallo,
- Ian Anderson,
- Daniel Holsgrove,
- Carole Chambers,
- Sandra Williams,
- Francesca Spickett-Jones,
- Marios C Papadopoulos,
- John Preston,
- Edward White,
- Adel Helmy,
- Sarah Ali,
- John Reid,
- Daniel Brown,
- Louis Taylor,
- Christopher Uff,
- Patrick Grover,
- Azra Banaras,
- Linetty Makawa,
- Anil Israni,
- Richard J Edwards,
- William Muirhead,
- Daniel Brooks,
- Debbie Brown,
- Ciaran Scott Hill,
- Kerry Smith,
- Beth Atkinson,
- Michelle Fawcett,
- Sifelani Tshuma,
- Oliver Kennion,
- Jo Howe,
- James J M Loan,
- Philip Clatworthy,
- Claire Hudson,
- Rebecca Hodnett,
- Madalina Roman,
- Mary Sikaonga,
- Elaine Kinsella,
- Mario Teo,
- Venetia Giannakaki,
- James Loan,
- Lauren Harris,
- Jack Wildman,
- Emmanuel Chavredakis,
- Nihal Gurusinghe,
- Alex Rossdeutsch,
- Anthony Wiggins,
- Giannis Sokratous,
- Lucie Ferguson,
- Shakeelah Patel,
- Sonia Raj,
- Oishik Raha,
- Janneke van Beijnum,
- Pragnesh Bhatt,
- Anna Bjornson,
- Nicole Broomes,
- Alistair Bullen,
- Julian Cahill,
- Mihai Danciut,
- Ronneil Digpal,
- Ioannis Fouyas,
- Lauren S Harris,
- Sohail Majeed,
- Matthias Radatz,
- Oliver Wroe Wright,
- Jessica Teasdale,
- Michelle Coakley,
- Drahoslav Sokol,
- Chandru Kaliaperumal,
- Mairi MacDonald,
- Sarah Risbridger,
- Siobhan Kearney,
- Ellaine Bosetta,
- Thomas Doke,
- Sonny Coskuner,
- Christine Kamara,
- Jonathan Gardner,
- Imron Hamina,
- Kishor Chaudhari,
- Liliana Chapas,
- Karen Caldwell,
- Sarah Holland,
- Tamara Tajsic,
- Rachael Dore,
- Taya Anderson,
- Shelley Mayor,
- Laura O'Malley,
- Samantha Glover,
- Janice Irvine,
- Annika Walch,
- Farah Muir,
- Eng Tah Goh,
- Andrew McDarby,
- Michelle Bates,
- Rebecca Hancox,
- Claudia Kate Auyeung,
- Elizabeth Goff,
- Deanna Stephens,
- Borislava Borislavova,
- Ruth Worner,
- Sandeep Buddha,
- Lisa Tucker,
- Sandra Dymond,
- Andrew Mallick,
- Janneke van Beijnum,
- Dymona McAleer,
- Belinda Gunning,
- Emma Clarkson,
- Cathy Stoneley,
- Jibril Osman Farah,
- Niamh Bohnacker,
- Rosette Marimon,
- Lydia Parker,
- Puneet Sharma,
- Oliver Wroe Wright,
- Dan Holsgrove,
- Danielle McLaughlan,
- Tracey Marsden,
- Kathryn Cawley,
- Hellen Raffalli,
- Imedla Mayor,
- Dipek Ram,
- Rebecca Keeping,
- Katie Hennessy,
- Ammar Kadhim,
- Md Moidul Islam,
- Manjunath Prasad,
- Cheryl Webster,
- Vicky Slater,
- Saffnan Mohamed,
- Saba Raza Knight,
- Terri-Louise Cromie,
- Allan Brown,
- Ruth Pennington,
- Charlene Campbell,
- Anthony Ghosh,
- Teresa Fitzpatrick,
- Mohammed Patel,
- Winnington Ruiz,
- Mirriam Taylor,
- Divina Anyog,
- Katarzyna Tluchowska,
- Jackson Nolasco,
- Kleopatra Angelopoulou,
- Bethany Welch,
- Ida Ponce,
- Lucy Bailey,
- Mia Marsden,
- Angelene Cope,
- Deepthy Blesson,
- Rachel Sutton,
- Mary Kambafwile,
- Jade McAndrew
Affiliations
- Khalid Hamandi
- 4 Department of Neurology, University Hospital of Wales, Cardiff, UK
- Julie Woodfield
- 1 Translational Neurosurgery, The University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, UK
- Smriti Agarwal
- Department of Stroke Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Richard Edwards
- 1Department of Public Health, University of Otago, Wellington, New Zealand
- John Williamson
- Department of Neurology, The Walton Centre Foundation NHS Trust, Liverpool, UK
- Ravindran Visagan
- 1 Emergency Department, Guy’s and Saint Thomas` NHS Foundation Trust, London, UK
- Rustam Al-Shahi Salman
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Howard Brydon
- Diederik Bulters
- 2 Neurosurgery, Wessex Neurological Centre, Southampton, Southampton, UK
- Dawn Hennigan
- Paul Leach
- Conor Mallucci
- Alder Hey Children’s Hospital, Liverpool, UK
- Nitin Mukerji
- Department of Neurosurgery, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK
- Marios Papadopoulos
- Nicholas Ross
- Department of Neurosurgery, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
- Martin Tisdall
- Department of Neurosurgery, Great Ormond Street Hospital, London, UK
- Carole Turner
- 7 Surgery Theme, Cambridge Clinical Trials Unit, Cambridge, UK
- Shungu Ushewokunze
- Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, UK
- Raghu Vindlacheruvu
- Queen’s Hospital, Romford, UK
- Paul Brennan
- consultant clinical geneticist
- Phil White
- 22 Institute for Ageing & Health, Newcastle University, Newcastle Upon Tyne, UK
- Sophie Hunter
- Karen Coy
- 4 Centre for Children’s Burns Research, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Julia Wade
- Population Health Sciences, Univeristy of Bristol, Bristol, UK
- James Stewart
- 1 Royal Marsden Hospital NHS Trust, London, UK
- Tom Hughes
- Football Medicine and Science Department, Manchester United Football Club, Manchester, UK
- Laura Forsyth
- 2 Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK
- Kirsty Harkness
- 1 Neuroscience, The University of Sheffield, Sheffield, Sheffield, UK
- David White
- Geriatric Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
- Rupal Shah
- general practitioner partner
- Sanjay Bhate
- 2 Fergus Robertson: Neuroradiology. Sanjay Bhate: Neurology, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK
- Neil Kitchen
- Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, UK
- Peter J Hutchinson
- Academic Neurosurgery, University of Cambridge, Cambridge, UK
- Emanuel Cirstea
- Ramesh Nair
- 2 Department of Neurosurgery, Charing Cross Hospital, London, UK
- Rebecca Hall
- 1Roseberry Medical Centre Loughborough, UK
- Varduhi Cahill
- Department of Neurology, University Hospitals Birmingham
- Tom Hayton
- Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Silvia Tarantino
- 4Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital and University of Cambridge
- Christin Eltze
- 2Great Ormond Street Hospital
- Jack Lee
- Centre for Clinical Research and Biostatistics, Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People`s Republic of China
- Arlo Whitehouse
- Daniel Walsh
- Department of Neurosurgery, King`s College Hospital NHS Foundation Trust, London, UK
- Jacqueline Stephen
- 3 Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, UK
- Nicola Phillips
- 1 Postgraduate Healthcare Sciences, Cardiff University, Cardiff, UK
- Steff Lewis
- Edinburgh Clinical Trials Unit, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Susan Davies
- Hepatology, Addenbrooke`s Hospital, Cambridge, UK
- Mathew Guilfoyle
- Department of Neurosurgery, Box 166, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
- Peter S Hall
- Institute of Cancer and Genetics, The University of Edinburgh, Edinburgh, UK
- Andrew Stoddart
- Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, UK
- Francesca Colombo
- 1 Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Lombardia, Italy
- Emma Richards
- ENT, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Greg James
- Sarah Illingworth
- 2London Metropolitan University
- William B Lo
- Andrew Bacon
- Professor of Global and Armed Forces Health, University of Chester, Chester, UK
- Vijeya Ganesan
- 3 Neurosciences Unit, UCL Institute of Child Health, London, UK
- Sabina Patel
- 3Core Discovery Technology Group, GlaxoSmithKline, Stevenage, UK
- Aileen R Neilson
- Health Economics Research Unit, University of Aberdeen, Aberdeen, UK
- Felicia Jennings
- Saba Raza-Knight
- 1Neurosciences Division, Addenbrooke`s Hospital, Cambridge, UK
- Andrew Brodbelt
- Aswin Chari
- Department of Neurosurgery, Great Ormond Street Hospital, London, UK
- Hasan Asif
- Ian Kamaly-Asl
- Milan Makwana
- Zubair Tahir
- Allan MacRaild
- 12 Emergency Medicine Research Group Edinburgh (EMERGE), NHS Lothian, Edinburgh, UK
- Rustam Al-Shahi Salman
- 9 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Grace Vassallo
- 22Department of Paediatric Neurology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
- Ian Anderson
- University of Manchester Manchester, UK
- Daniel Holsgrove
- Centre for Clinical Neurosciences, Salford Royal Hospital Manchester, Salford, UK
- Carole Chambers
- Sandra Williams
- 4 Tharawal Aboriginal Corporation, Sydney, New South Wales, Australia
- Francesca Spickett-Jones
- The Scar Free Foundation Centre for Children’s Burn Research, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Marios C Papadopoulos
- 1Department of Neurosurgery, St George`s Hospital, London, UK
- John Preston
- School of Civil Engineering and the Environment, University of Southampton, Southampton, UK
- Edward White
- Center for Interdisciplinary Research on AIDS, Yale University, School of Public Health, New Haven, Connecticut, USA
- Adel Helmy
- Addenbrooke’s Hosptial, Cambridge, UK
- Sarah Ali
- 2Royal Alexandra Children’s Hospital
- John Reid
- Borders General Hospital, Melrose, UK
- Daniel Brown
- Louis Taylor
- Oxford University Hospitals NHS Trust, Oxford, UK
- Christopher Uff
- 2Department of Neurosurgery, The Royal London Hospital, London, UK
- Patrick Grover
- National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK
- Azra Banaras
- Linetty Makawa
- Anil Israni
- Paediatric Neurology, Paediatric Neurology Alder Hey Children Hospital, Liverpool, UK
- Richard J Edwards
- 3Therapeutics and Cardiac Research Team, Freeman Hospital, Newcastle upon Tyne, UK
- William Muirhead
- Daniel Brooks
- 2Neuroscience Research Australia, University of New South Wales, Sydney, NSW, Australia
- Debbie Brown
- Ciaran Scott Hill
- chartered physiotherapist and fourth year medical student
- Kerry Smith
- 10 Information Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
- Beth Atkinson
- Michelle Fawcett
- Sifelani Tshuma
- Oliver Kennion
- Jo Howe
- College of Health and Life Sciences, Aston University, Birmingham, UK
- James J M Loan
- Division of Clinical Neurosciences, NHS Lothian, Edinburgh, UK
- Philip Clatworthy
- clinical research fellow
- Claire Hudson
- 2University of Bristol
- Rebecca Hodnett
- 1North Bristol Trust
- Madalina Roman
- 2Sheffield Teaching Hospitals NHS Trust
- Mary Sikaonga
- 2Sheffield Teaching Hospitals NHS Trust
- Elaine Kinsella
- 2Edinburgh Clinical Trials unit,Edinburgh University
- Mario Teo
- Department of Neurosurgery, North Bristol NHS Trust, Bristol, UK
- Venetia Giannakaki
- James Loan
- Lauren Harris
- Jack Wildman
- Department of Neurosurgery, Southmead Hospital, Bristol, UK
- Emmanuel Chavredakis
- Department of Neurosurgery, Walton Centre NHS Foundation Trust, Liverpool, UK
- Nihal Gurusinghe
- Department of Neurosurgery, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
- Alex Rossdeutsch
- Royal Hallamshire Hospital, Sheffield, UK
- Anthony Wiggins
- Giannis Sokratous
- Lucie Ferguson
- James Cook University Hospital, Middlesbrough, UK
- Shakeelah Patel
- Lancashire Teaching Hospital NHS Foundation Trust, Preston, UK
- Sonia Raj
- Lancashire Teaching Hospital NHS Foundation Trust, Preston, UK
- Oishik Raha
- Imperial Stroke Centre, Imperial College Healthcare NHS Trust, London, UK
- Janneke van Beijnum
- Neurosurgery, University Hospital of Wales, Cardiff, UK
- Pragnesh Bhatt
- Aberdeen Royal Infirmary, Aberdeen, UK
- Anna Bjornson
- Hull Royal Infirmary, Kingston upon Hull, UK
- Nicole Broomes
- University Hospital Southampton NHS Foundation Trust Wessex Neurological Centre, Southampton, UK
- Alistair Bullen
- Edinburgh Clinical Trials Unit, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
- Julian Cahill
- National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK
- Mihai Danciut
- Hull Royal Infirmary, Kingston upon Hull, UK
- Ronneil Digpal
- University Hospital Southampton NHS Foundation Trust Wessex Neurological Centre, Southampton, UK
- Ioannis Fouyas
- Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh, UK
- Lauren S Harris
- Queen’s Hospital, Romford, UK
- Sohail Majeed
- Aberdeen Royal Infirmary, Aberdeen, UK
- Matthias Radatz
- National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK
- Oliver Wroe Wright
- King’s College Hospital, London, UK
- Jessica Teasdale
- Michelle Coakley
- Drahoslav Sokol
- Chandru Kaliaperumal
- Mairi MacDonald
- Sarah Risbridger
- Siobhan Kearney
- Ellaine Bosetta
- Thomas Doke
- Sonny Coskuner
- Christine Kamara
- Jonathan Gardner
- Imron Hamina
- Kishor Chaudhari
- Liliana Chapas
- Karen Caldwell
- Sarah Holland
- Tamara Tajsic
- Rachael Dore
- Taya Anderson
- Shelley Mayor
- Laura O'Malley
- Samantha Glover
- Janice Irvine
- Annika Walch
- Farah Muir
- Eng Tah Goh
- Andrew McDarby
- Michelle Bates
- Rebecca Hancox
- Claudia Kate Auyeung
- Elizabeth Goff
- Deanna Stephens
- Borislava Borislavova
- Ruth Worner
- Sandeep Buddha
- Lisa Tucker
- Sandra Dymond
- Andrew Mallick
- Janneke van Beijnum
- Dymona McAleer
- Belinda Gunning
- Emma Clarkson
- Cathy Stoneley
- Jibril Osman Farah
- Niamh Bohnacker
- Rosette Marimon
- Lydia Parker
- Puneet Sharma
- Oliver Wroe Wright
- Dan Holsgrove
- Danielle McLaughlan
- Tracey Marsden
- Kathryn Cawley
- Hellen Raffalli
- Imedla Mayor
- Dipek Ram
- Rebecca Keeping
- Katie Hennessy
- Ammar Kadhim
- Md Moidul Islam
- Manjunath Prasad
- Cheryl Webster
- Vicky Slater
- Saffnan Mohamed
- Saba Raza Knight
- Terri-Louise Cromie
- Allan Brown
- Ruth Pennington
- Charlene Campbell
- Anthony Ghosh
- Teresa Fitzpatrick
- Mohammed Patel
- Winnington Ruiz
- Mirriam Taylor
- Divina Anyog
- Katarzyna Tluchowska
- Jackson Nolasco
- Kleopatra Angelopoulou
- Bethany Welch
- Ida Ponce
- Lucy Bailey
- Mia Marsden
- Angelene Cope
- Deepthy Blesson
- Rachel Sutton
- Mary Kambafwile
- Jade McAndrew
- DOI
- https://doi.org/10.1136/bmjopen-2023-075187
- Journal volume & issue
-
Vol. 13,
no. 8
Abstract
Introduction The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was ‘Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?’ This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysis We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and dissemination This study was approved by the Yorkshire and The Humber—Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration number ISRCTN41647111.