TY - JOUR
T1 - Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA)
T2 - A multicentre, non-blinded, randomised trial
AU - Mohr, J. P.
AU - Parides, Michael K.
AU - Stapf, Christian
AU - Moquete, Ellen
AU - Moy, Claudia S.
AU - Overbey, Jessica R.
AU - Salman, Rustam Al Shahi
AU - Vicaut, Eric
AU - Young, William L.
AU - Houdart, Emmanuel
AU - Cordonnier, Charlotte
AU - Stefani, Marco A.
AU - Hartmann, Andreas
AU - Von Kummer, Rüdiger
AU - Biondi, Alessandra
AU - Berkefeld, Joachim
AU - Klijn, Catharina J.M.
AU - Harkness, Kirsty
AU - Libman, Richard
AU - Barreau, Xavier
AU - Moskowitz, Alan J.
N1 - Funding Information:
This paper is dedicated in memoriam to our colleague and friend William L Young, in recognition of his contribution to brain arteriovenous malformations research and to the ARUBA trial. We thank patients who participate in this trial. This trial is funded internationally by the National Institute of Neurological Diosorders and Stroke of the US National Institutes of Health via cooperative agreements U01NS051483 (CCC; J.P.Mohr, PI) and U01 NS051566 (DCC; A.J. Moskowitz, PI). No commercial funding sources have been involved. ARUBA has been officially adopted by the UK Stroke Research Network and endorsed by the Société Française Neurovasculaire (SFNV). Initial results have been presented at the European Stroke Conference; London, UK; May 28–31, 2013.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(13)62302-8
DO - 10.1016/S0140-6736(13)62302-8
M3 - Article
C2 - 24268105
AN - SCOPUS:84893842883
SN - 0140-6736
VL - 383
SP - 614
EP - 621
JO - The Lancet
JF - The Lancet
IS - 9917
ER -