title: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.
abstract: BACKGROUND
  The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy.
  
  
  METHODS
  Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181.
  
  
  RESULTS
  Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management.
  
  
  CONCLUSIONS
  The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.
  
  
  BACKGROUND
  National Institutes of Health, National Institute of Neurological Disorders and Stroke.
authors.affiliation: The Neurological Institute, Columbia University Medical Center, New York, NY, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mohr
authors.affiliation: International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parides
authors.affiliation: The Neurological Institute, Columbia University Medical Center, New York, NY, USA; Department of Neurology, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France; DHU NeuroVasc, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France. Electronic address: christian.stapf@lrb.aphp.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Stapf
authors.affiliation: International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Moquete
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Moy
authors.affiliation: International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Overbey
authors.affiliation: Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Rustam
authors.initials: R
authors.lastname: Al-Shahi Salman
authors.affiliation: Unité de Recherche Clinique, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.affiliation: Department of Neuroradiology, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Houdart
authors.affiliation: Department of Neurology, CHRU Lille, Université Lille Nord de France, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: Department of Neurology and Neurosurgery, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Stefani
authors.affiliation: Charité-Universitätsmedizin Berlin Berlin, Germany; Department of Neurology, Klinikum Frankfurt/Oder, Frankfurt/Oder Oder, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Neuroradiology, University Hospital Dresden, Dresden, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Kummer
authors.affiliation: Department of Neuroradiology and Endovascular Therapy, Jean Minjoz Hospital, University of Franche Comté, Besançon, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Department of Neuroradiology, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Berkefeld
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center, Utrecht, Netherlands.
authors.forename: Catharina J M
authors.initials: CJ
authors.lastname: Klijn
authors.affiliation: Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Harkness
authors.affiliation: Department of Neurology, North Shore Long Island Jewish Medical Center, New Hyde Park, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Libman
authors.affiliation: Department of Diagnostic and Interventional Neuroimaging, CHU Pellegrin, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Barreau
authors.affiliation: International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Moskowitz
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D003131:Combined Modality Therapy; D004621:Embolization, Therapeutic / Q000379:methods; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000379:methods; D011446:Prospective Studies; D016634:Radiosurgery / Q000379:methods; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D055815:Young Adult