{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:14:33Z","timestamp":1755796473929,"version":"3.44.0"},"reference-count":54,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title>\n<jats:p>The top priority for research into symptomatic cerebral cavernous malformation (also known as brain cavernoma) is whether to have medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-2\"><jats:title>Objectives<\/jats:title>\n<jats:p>The primary objective was to assess the feasibility of performing a definitive randomised trial addressing this top priority. The secondary objectives were to set up a collaboration involving patient advocacy organisations and clinicians in the United Kingdom and Ireland; perform a QuinteT Recruitment Intervention to identify facilitators and address barriers to recruitment; and conduct a pilot randomised trial with \u224860 participants.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title>\n<jats:p>Prospective, randomised, open-label, assessor-blinded, parallel-group trial. A mixed-methods QuinteT Recruitment Intervention analysed sites\u2019 screening logs and qualitative data from audio-recorded recruitment discussions, interviews with healthcare professionals and patients, investigator workshops and observation of meetings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title>\n<jats:p>Neuroscience hospitals in the United Kingdom and Ireland.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title>\n<jats:p>We aimed to recruit \u224860 people of any age, gender and ethnicity who had mental capacity, resided in the United Kingdom\/Ireland, and had a brain cavernoma that had caused symptoms due to intracranial haemorrhage, non-haemorrhagic progressive\/persistent focal neurological deficit or epileptic seizure(s).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title>\n<jats:p>We identified and addressed barriers and facilitators to optimise informed consent and recruitment. Computerised, web-based randomisation assigned participants (1\u2005:\u20051) to treatment of their symptomatic brain cavernoma with medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone. Assignment was open to investigators, participants and carers but not clinical outcome event adjudicators.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title>\n<jats:p>Feasibility outcomes included site engagement, recruitment, choice of surgical management, retention, adherence, data quality, clinical outcome event rate and protocol implementation. The primary clinical outcome was symptomatic intracranial haemorrhage or new persistent\/progressive non-haemorrhagic focal neurological deficit due to brain cavernoma or intervention during \u2265 6 months of follow-up.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title>\n<jats:p>Investigators screened 511 patients at 28\/40 (70%) sites in the United Kingdom: 322 (63%) eligible, 202 (63%) approached, 96 (48%) uncertain about whether to have intervention and 72 participants [median age was 51 years (interquartile range 39\u201359), 41 (57%) female, 66 (92%) white, 56 (78%) with prior intracranial haemorrhage and 28 (39%) with prior epileptic seizure] were randomly assigned to medical management and intervention (<jats:italic>n<\/jats:italic>\u2005=\u200536; 12 to neurosurgical resection and 24 to stereotactic radiosurgery) or medical management alone (<jats:italic>n<\/jats:italic>\u2005=\u200536) after a recruitment extension. Sixty-seven participants completed follow-up (retention 93%), and adherence was 91%. Barriers to recruitment included usual-care practices and logistical issues with stereotactic radiosurgery, whereas facilitators were neurosurgeons\u2019 preparedness to offer intervention to more people than in usual care, multidisciplinary team equipoise and presenting the study as a solution to equipoise. The primary clinical outcome occurred in 2\/33 assigned to medical management and intervention and 2\/34 assigned to medical management alone. There were no deaths or serious adverse events.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-9\"><jats:title>Limitations<\/jats:title>\n<jats:p>We could not activate sites in Ireland. The generalisability of our findings outside the United Kingdom is unknown.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-10\"><jats:title>Conclusions<\/jats:title>\n<jats:p>This pilot randomised trial identified facilitators and barriers to recruitment, exceeded its recruitment target and met some feasibility metrics.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-11\"><jats:title>Future work<\/jats:title>\n<jats:p>A definitive randomised trial will need extensive engagement from international funders and networks of clinicians, researchers and patient groups to recruit 590\u20131900 participants.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-12\"><jats:title>Funding<\/jats:title>\n<jats:p>This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128694.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/gjrs5321","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T07:40:53Z","timestamp":1742542853000},"page":"1-24","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) versus medical management alone for symptomatic brain cavernoma: the CARE pilot RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-9222","authenticated-orcid":true,"given":"Rustam","family":"Al-Shahi Salman","sequence":"first","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1655-5970","authenticated-orcid":true,"given":"Neil","family":"Kitchen","sequence":"additional","affiliation":[{"name":"The National Hospital for Neurology and Neurosurgery, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-0392","authenticated-orcid":true,"given":"Laura","family":"Forsyth","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-6216","authenticated-orcid":true,"given":"Vijeya","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Developmental Neurosciences Department, Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-7841","authenticated-orcid":true,"given":"Peter S","family":"Hall","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6733-6938","authenticated-orcid":true,"given":"Kirsty","family":"Harkness","sequence":"additional","affiliation":[{"name":"National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2796-1835","authenticated-orcid":true,"given":"Peter JA","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Addenbrooke\u2019s Hospital, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1210-2314","authenticated-orcid":true,"given":"Steff C","family":"Lewis","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3342-0615","authenticated-orcid":true,"given":"Matthias WR","family":"Radatz","sequence":"additional","affiliation":[{"name":"National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-4890","authenticated-orcid":true,"given":"Carole","family":"Turner","sequence":"additional","affiliation":[{"name":"Addenbrooke\u2019s Hospital, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-6477","authenticated-orcid":true,"given":"Julia","family":"Wade","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1310-0238","authenticated-orcid":true,"given":"David CS","family":"White","sequence":"additional","affiliation":[{"name":"Cavernoma Alliance UK, Watlington, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6007-6013","authenticated-orcid":true,"given":"Philip M","family":"White","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University and Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"key2025081812073100_ref1-bib1","doi-asserted-by":"crossref","first-page":"e075187","DOI":"10.1136\/bmjopen-2023-075187","article-title":"Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma \u2013 protocol for the cavernomas: a randomised effectiveness (CARE) pilot trial","volume":"13","author":"Loan","year":"2023","journal-title":"BMJ Open"},{"key":"key2025081812073100_ref2-bib2","doi-asserted-by":"crossref","first-page":"b3016","DOI":"10.1136\/bmj.b3016","article-title":"Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis","volume":"339","author":"Morris","year":"2009","journal-title":"BMJ"},{"key":"key2025081812073100_ref3-bib3","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1161\/STROKEAHA.108.515544","article-title":"Hemorrhage from cavernous malformations of the brain: definition and reporting standards","volume":"39","author":"Al-Shahi Salman","year":"2008","journal-title":"Stroke"},{"key":"key2025081812073100_ref4-bib4","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1161\/01.STR.0000069018.90456.C9","article-title":"Prospective, population-based detection of intracranial vascular malformations in adults: the Scottish Intracranial Vascular Malformation Study (SIVMS)","volume":"34","author":"Al-Shahi","year":"2003","journal-title":"Stroke"},{"key":"key2025081812073100_ref5-bib5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S1474-4422(15)00303-8","article-title":"Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data","volume":"15","author":"Horne","year":"2016","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref6-bib6","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1212\/WNL.0b013e3182190f37","article-title":"Seizure risk from cavernous or arteriovenous malformations: prospective population-based study","volume":"76","author":"Josephson","year":"2011","journal-title":"Neurology"},{"key":"key2025081812073100_ref7-bib7","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1161\/STROKEAHA.108.539528","article-title":"Economic burden of intracranial vascular malformations in adults: prospective population-based study","volume":"40","author":"Miller","year":"2009","journal-title":"Stroke"},{"key":"key2025081812073100_ref8-bib8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S1474-4422(07)70053-4","article-title":"Genetics of cavernous angiomas","volume":"6","author":"Labauge","year":"2007","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref9-bib9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1159\/000480125","article-title":"Cerebral cavernous malformations: patient-reported outcome validates conservative management","volume":"44","author":"Bicalho","year":"2017","journal-title":"Cerebrovasc Dis"},{"key":"key2025081812073100_ref10-bib10","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1212\/WNL.0000000000000684","article-title":"Outcome after surgical or conservative management of cerebral cavernous malformations","volume":"83","author":"Moultrie","year":"2014","journal-title":"Neurology"},{"key":"key2025081812073100_ref11-bib11","doi-asserted-by":"crossref","first-page":"e1971","DOI":"10.1212\/WNL.0000000000008521","article-title":"Stereotactic radiosurgery for cerebral cavernous malformations: a systematic review","volume":"93","author":"Poorthuis","year":"2019","journal-title":"Neurology"},{"key":"key2025081812073100_ref12-bib12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10143-021-01591-5","article-title":"Surgery for cerebral cavernous malformations: a systematic review and meta-analysis","volume":"45","author":"Harris","year":"2022","journal-title":"Neurosurg Rev"},{"key":"key2025081812073100_ref13-bib13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00701-013-1621-4","article-title":"Comparative studies of the diagnosis and treatment of cerebral cavernous malformations in adults: systematic review","volume":"155","author":"Poorthuis","year":"2013","journal-title":"Acta Neurochir (Wien)"},{"volume-title":"Guidelines for the Management of Cerebral Cavernous Malformations in Adults","year":"2012","author":"Samarasekera","key":"key2025081812073100_ref14-bib14"},{"key":"key2025081812073100_ref15-bib15","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/neuros\/nyx091","article-title":"Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the Angioma Alliance Scientific Advisory Board clinical experts panel","volume":"80","author":"Akers","year":"2017","journal-title":"Neurosurgery"},{"key":"key2025081812073100_ref16-bib16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.eplepsyres.2017.08.016","article-title":"Radiosurgery for epilepsy: systematic review and International Stereotactic Radiosurgery Society (ISRS) practice guideline","volume":"137","author":"McGonigal","year":"2017","journal-title":"Epilepsy Res"},{"key":"key2025081812073100_ref17-bib17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S1474-4422(16)00039-9","article-title":"Top ten research priorities for brain and spine cavernous malformations","volume":"15","author":"Al-Shahi Salman","year":"2016","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref18-bib18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1136\/bmj.39070.527986.68","article-title":"When are randomised trials unnecessary? Picking signal from noise","volume":"334","author":"Glasziou","year":"2007","journal-title":"BMJ"},{"key":"key2025081812073100_ref19-bib19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1136\/jnnp-2013-307349","article-title":"Treatment of cerebral cavernous malformations: a systematic review and meta-regression analysis","volume":"85","author":"Poorthuis","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key2025081812073100_ref20-bib20","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1177\/1747493019851290","article-title":"Radiosurgical, neurosurgical, or no intervention for cerebral cavernous malformations: a decision analysis","volume":"14","author":"Rinkel","year":"2019","journal-title":"Int J Stroke"},{"key":"key2025081812073100_ref21-bib21","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1227\/01.NEU.0000346269.59554.DB","article-title":"Long-term outcome of patients with multiple cerebral cavernous malformations","volume":"65","author":"Kivelev","year":"2009","journal-title":"Neurosurgery"},{"key":"key2025081812073100_ref22-bib22","first-page":"5","article-title":"Place of the surgery in the management of brainstem cavernomas. Results of a multicentric study","volume":"49","author":"Esposito","year":"2003","journal-title":"Neurochirurgie"},{"key":"key2025081812073100_ref23-bib23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3171\/jns.2003.99.1.0031","article-title":"Deep and brainstem cavernomas: a consecutive 8-year series","volume":"99","author":"Mathiesen","year":"2003","journal-title":"J Neurosurg"},{"key":"key2025081812073100_ref24-bib24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1080\/02688690802354210","article-title":"Does conservative management for brain stem cavernomas have better long-term outcome?","volume":"22","author":"Tarnaris","year":"2008","journal-title":"Br J Neurosurg"},{"key":"key2025081812073100_ref25-bib25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jocn.2009.06.009","article-title":"Brain stem cavernous malformations","volume":"17","author":"Huang","year":"2010","journal-title":"J Clin Neurosci"},{"key":"key2025081812073100_ref26-bib26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.7887\/jcns.24.108","article-title":"Natural history of symptomatic cavernous malformations and results of surgery","volume":"24","author":"Kida","year":"2015","journal-title":"Jpn J Neurosurg"},{"key":"key2025081812073100_ref27-bib27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2176\/nmc.38.suppl_255","article-title":"Cerebral cavernous malformations: serial magnetic resonance imaging findings in patients with and without gamma knife surgery","volume":"38","author":"Yoon","year":"1998","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"key2025081812073100_ref28-bib28","doi-asserted-by":"crossref","first-page":"982","DOI":"10.3171\/2013.12.JNS13990","article-title":"Stereotactic radiosurgery of brainstem cavernous malformations: a systematic review and meta-analysis","volume":"120","author":"Lu","year":"2014","journal-title":"J Neurosurg"},{"key":"key2025081812073100_ref30-bib30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1745-6215-12-64","article-title":"A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials","volume":"12","author":"Raymond","year":"2011","journal-title":"Trials"},{"key":"key2025081812073100_ref31-bib31","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S0140-6736(13)62302-8","article-title":"Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial","volume":"383","author":"Mohr","year":"2014","journal-title":"Lancet"},{"key":"key2025081812073100_ref32-bib32","doi-asserted-by":"crossref","first-page":"486","DOI":"10.3171\/2015.6.JNS15619","article-title":"Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials","volume":"126","author":"Magro","year":"2017","journal-title":"J Neurosurg"},{"key":"key2025081812073100_ref33-bib33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1745-6215-15-5","article-title":"Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials","volume":"15","author":"Donovan","year":"2014","journal-title":"Trials"},{"key":"key2025081812073100_ref34-bib34","doi-asserted-by":"crossref","first-page":"100335","DOI":"10.1016\/j.conctc.2019.100335","article-title":"Treatment preference and recruitment to pediatric RCTs: a systematic review","volume":"14","author":"Beasant","year":"2019","journal-title":"Contemp Clin Trials Commun"},{"key":"key2025081812073100_ref35-bib35","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s13063-016-1391-4","article-title":"Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI)","volume":"17","author":"Donovan","year":"2016","journal-title":"Trials"},{"key":"key2025081812073100_ref36-bib36","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1136\/bmj.325.7367.766","article-title":"Quality improvement report: improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study","volume":"325","author":"Donovan","year":"2002","journal-title":"BMJ"},{"key":"key2025081812073100_ref37-bib37","doi-asserted-by":"crossref","first-page":"e1002147","DOI":"10.1371\/journal.pmed.1002147","article-title":"Conveying equipoise during recruitment for clinical trials: qualitative synthesis of clinicians\u2019 practices across six randomised controlled trials","volume":"13","author":"Rooshenas","year":"2016","journal-title":"PLOS Med"},{"key":"key2025081812073100_ref38-bib38","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1745-6215-12-78","article-title":"Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK\/07\/011)","volume":"12","author":"Paramasivan","year":"2011","journal-title":"Trials"},{"key":"key2025081812073100_ref39-bib39","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jclinepi.2018.10.004","article-title":"By-Band-Sleeve Study Group. The QuinteT Recruitment Intervention supported five randomized trials to recruit to target: a mixedmethods evaluation","volume":"106","author":"Rooshenas","year":"2019","journal-title":"J Clin Epidemiol"},{"key":"key2025081812073100_ref40-bib40","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1474-4422(24)00096-6","article-title":"Medical management and surgery versus medical management alone for symptomatic cerebral cavernous malformation (CARE): a feasibility study and randomised, open, pragmatic, pilot phase trial","volume":"23","author":"CARE Pilot Trial Collaboration","year":"2024","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref41-bib41","doi-asserted-by":"crossref","first-page":"102557","DOI":"10.1016\/j.eclinm.2024.102557","article-title":"Addressing barriers and identifying facilitators to support informed consent and recruitment in the Cavernous malformations A Randomised Effectiveness (CARE) pilot phase trial: insights from the integrated QuinteT Recruitment Intervention (QRI)","volume":"71","author":"Wade","year":"2024","journal-title":"EClinicalMedicine"},{"key":"key2025081812073100_ref42-bib42","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1186\/s13063-023-07414-w","article-title":"Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions","volume":"24","author":"Lorenc","year":"2023","journal-title":"Trials"},{"key":"key2025081812073100_ref43-bib43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1161\/STROKEAHA.123.044068","article-title":"Trial readiness of cavernous malformations with symptomatic hemorrhage, Part I: event rates and clinical outcome","volume":"55","author":"Flemming","year":"2024","journal-title":"Stroke"},{"key":"key2025081812073100_ref44-bib44","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S1474-4422(24)00321-1","article-title":"Considerations for future trials in cerebral cavernous malformations","volume":"23","author":"Cenzato","year":"2024","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref45-bib45","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/S1474-4422(24)00322-3","article-title":"Considerations for future trials in cerebral cavernous malformations","volume":"23","author":"Alawieh","year":"2024","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref46-bib46","first-page":"965","article-title":"Considerations for future trials in cerebral cavernous malformations \u2013 authors\u2019 reply","volume":"23","author":"CARE Pilot Trial Collaboration","year":"2024","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref47-bib47","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jamaneurol.2017.0439","article-title":"Population-based prevalence of cerebral cavernous malformations in older adults: Mayo Clinic study of aging","volume":"74","author":"Flemming","year":"2017","journal-title":"JAMA Neurol"},{"key":"key2025081812073100_ref48-bib48","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/STROKEAHA.121.035654","article-title":"Molecular biomarkers and drug targets in brain arteriovenous and cavernous malformations: where are we?","volume":"53","author":"Venugopal","year":"2022","journal-title":"Stroke"},{"key":"key2025081812073100_ref49-bib49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1161\/CIRCULATIONAHA.114.010403","article-title":"Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation","volume":"131","author":"Gibson","year":"2015","journal-title":"Circulation"},{"key":"key2025081812073100_ref50-bib50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1474-4422(22)00409-4","article-title":"Safety and efficacy of propranolol for treatment of familial cerebral cavernous malformations (Treat_CCM): a randomised, open-label, blinded-endpoint, phase 2 pilot trial","volume":"22","author":"Lanfranconi","year":"2023","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref51-bib51","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S1474-4422(19)30231-5","article-title":"Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis","volume":"18","author":"Zuurbier","year":"2019","journal-title":"Lancet Neurol"},{"key":"key2025081812073100_ref52-bib52","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1161\/STROKEAHA.121.037009","article-title":"Association between beta-blocker or statin drug use and the risk of hemorrhage from cerebral cavernous malformations","volume":"53","author":"Zuurbier","year":"2022","journal-title":"Stroke"},{"key":"key2025081812073100_ref53-bib53","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1186\/s13063-019-3664-1","article-title":"Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols","volume":"20","author":"Park","year":"2019","journal-title":"Trials"},{"key":"key2025081812073100_ref54-bib54","doi-asserted-by":"crossref","first-page":"e00011","DOI":"10.1227\/neuopn.0000000000000011","article-title":"Comparative effectiveness of management by surgical resection vs observation for cerebral cavernous malformations: a matched propensity score analysis","volume":"3","author":"Han","year":"2022","journal-title":"Neurosurgery Open"},{"key":"key2025081812073100_ref55-bib55","doi-asserted-by":"crossref","first-page":"123471","DOI":"10.1016\/j.wneu.2024.11.054","article-title":"A review of neurosurgical randomized controlled trials in the Cochrane Database of Systematic Reviews: key findings and implications for future research","volume":"194","author":"Thompson","year":"2025","journal-title":"World Neurosurg"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2048643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/sites\/journalslibrary\/files\/journal_data\/GJRS5321\/GJRS5321.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2048643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T06:55:34Z","timestamp":1755500134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/GJRS5321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":54,"alternative-id":["10.3310\/GJRS5321"],"URL":"https:\/\/doi.org\/10.3310\/gjrs5321","relation":{},"ISSN":["2046-4924"],"issn-type":[{"type":"electronic","value":"2046-4924"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"09-2020","name":"contractual_start_date","label":"contractual_start_date","group":{"name":"article_history","label":"Article History"}},{"value":"05-2024","name":"editorial_review_begun","label":"editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"04-2025","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}