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Lancet. 2014 Feb 15;383(9917):614-21. doi: 10.1016/S0140-6736(13)62302-8. Epub 2013 Nov 20.

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.

Collaborators (211)

Mohr JP, Moskowitz AJ, Moquete E, Moy CS, Parides MK, Al-Shahi Salman R, Stapf C, Vicaut E, Young WL, Mohr JP, Marshall S, Ostapkovich N, Lord K, Stapf C, Buchbinder C, Moskowitz AJ, Parides MK, Moquete E, McDonald K, Estevez A, Varghese S, Overbey JR, Kumbarce E, Foo J, Vicaut E, Chamam A, Courrèges-Viaud M, Dert C, Fiedler U, Jouis V, Kabla S, Marchand S, Pena A, Rochaud V, Furie K, Davis BR, Hill MD, Jungreis C, Martin R, Samson D, Gilbert PR, Furlan A, Moy CS, Janis LS, Gilbert PR, Bousser MG, Caplan LR, Strother C, Weir BA, Schneble HM, Patel A, Meyers PM, Pile-Spellman J, Houdart E, Bresson D, George B, Saint-Maurice JP, Stapf C, Lejeune JP, Aguettaz P, Blond S, Cordonnier C, Leclerc X, Rossi C, Biondi A, Billon-Grand R, Moulin T, Barreau X, Marchal C, Michel V, Thévenoux A, Tedeschi I, Timsit S, Dam-Hieu P, Meriot P, Merrien FM, Nedelec AS, Nonent M, Nataf F, Calvet D, Touzé E, Trystram D, von Kummer R, Baumann M, Bodechtel U, Dzialowski I, Hentschel H, Kepplinger J, Pütz V, Schackert G, Wartenberg K, Hartmann A, Funk T, Schilling A, Wurm R, Berkefeld J, Braun H, Lorenz MW, Santos I, Seifert V, Wolff R, Meisel J, Herrmann E, Hohaus C, Minkus Y, Dichgans M, Brueckmann H, Dörr A, Fesl G, Muacevic A, Schichor C, Wollenweber F, Wowra BM, Zollver A, Schumacher M, Bergmann U, Hader C, Niesen WD, Taschner C, Velthoven-Wurster V, Wanke I, Hagedorn S, Kastrup O, Sandalcioglu I, Sure U, van der Worp HB, Klijn CJ, Berkelbach van der Sprenkel JW, Lo TH, van Dijk JM, Eshghi O, Luijckx GJ, Arnold M, Raabe A, Schroth G, Heldner M, Reinert M, Al-Shahi Salman R, Colam B, Erridge S, Sellar R, Steers J, White PM, Harkness K, Coley S, Hodgeson T, Richards E, Patel U, Mendelow AD, Gholkar A, Mitchell P, Gregson B, Nahser H, Javadpour M, Enevoldson P, White R, Molloy J, Hughes D, Sherrington C, Stefani MA, Fagundes Chaves ML, Finkelsztejn A, Roy D, Raymond J, Guilbert F, Darsaut T, Butcher K, Silva J, Klurfan P, Yoon BW, Kim JA, Jung S, Kim Y, Kim C, Libman R, Langer DJ, Mohr JP, Kitago T, Young WL, Lawton MT, Higashida R, Johnston SC, Feng L, Chen J, Ajani Z, Potrebic S, Wirkowski E, Pile-Spellman J, Brisman M, Jasen J, Kureshi I, Spiegel G, Silverman I, Koch S, Sacco RL, Chen M, Lee V, Prabhakaran S, Harrigan M, Brockington J, Zweilfer RM, Lopez JI, Biller J, Schneck M, Anderson D, Cullen S, Rao V, Moayeri N, Tse V, Bowles AP Jr, Nassr K.

Author information

1
The Neurological Institute, Columbia University Medical Center, New York, NY, USA.
2
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.
3
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.
4
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
5
Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
6
Unité de Recherche Clinique, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France.
7
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
8
Department of Neuroradiology, APHP-Hôpital Lariboisière, Univ Paris Diderot-Sorbonne Paris Cité, Paris, France.
9
Department of Neurology, CHRU Lille, Université Lille Nord de France, Lille, France.
10
Department of Neurology and Neurosurgery, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
11
Charité-Universitätsmedizin Berlin Berlin, Germany; Department of Neurology, Klinikum Frankfurt/Oder, Frankfurt/Oder Oder, Germany.
12
Department of Neuroradiology, University Hospital Dresden, Dresden, Germany.
13
Department of Neuroradiology and Endovascular Therapy, Jean Minjoz Hospital, University of Franche Comté, Besançon, France.
14
Department of Neuroradiology, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
15
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center, Utrecht, Netherlands.
16
Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
17
Department of Neurology, North Shore Long Island Jewish Medical Center, New Hyde Park, NY, USA.
18
Department of Diagnostic and Interventional Neuroimaging, CHU Pellegrin, Bordeaux, France.

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.

FINDINGS:

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.

INTERPRETATION:

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.

FUNDING:

National Institutes of Health, National Institute of Neurological Disorders and Stroke.

PMID:
24268105
PMCID:
PMC4119885
DOI:
10.1016/S0140-6736(13)62302-8
[Indexed for MEDLINE]
Free PMC Article

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