Functional impairments for outcomes in a randomized trial of unruptured brain AVMs
Abstract
Objective:
To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA).
Methods:
We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013.
Results:
After a median of 33.3 months of follow-up (interquartile range 16.3–49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11–0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04–0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001).
Conclusion:
Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades.
ClinicalTrials.gov identifier:
NCT00389181.
Classification of evidence:
This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.
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© 2017 American Academy of Neurology.
Publication History
Received: September 13, 2016
Accepted: June 13, 2017
Published online: September 6, 2017
Published in print: October 3, 2017
Disclosure
J. Mohr: NINDS ARUBA grant funding U01 NS051483. No other personal funding apart from reimbursement for attending meetings and honoraria for grand rounds presentations 2015 at Beth Israel New York City, University of Miami, University of Arizona (Tucson), and Houston TX; for 2016, only reimbursement for attending meetings. Donations made to Columbia Development Office in 2015 and 2016 from the Vital Projects Fund and Richard and Jenny Levine Foundation assisted in funding follow-up data after the discontinuation of NINDS funding in August 2013. J. Overbey: NINDS ARUBA grant UO1 NS51566 salary support as study statistician. R. von Kummer: salaried chief of university interventional neuroradiology in Dresden Germany; institution reimbursed from the grant for case enrollment. M. Stefani: salaried chief of university interventional neuroradiology Federal University of Rio Grande do Sul, Porto Alegre, Brazil; reimbursed by the grant for case enrollment from his center. R. Libman: salaried vice-chairman of Neurology, Long Island Jewish Hospital, New Hyde Park, NY, reimbursed from the grant for case enrollment. C. Stapf: NINDS ARUBA grant UO1 NS51566, coprincipal investigator. M. Parides: NINDS ARUBA grant UO1 NS51566, principal statistician for the Statistical Coordinating Center. J. Pile-Spellman: voluntary staff interventional neuroradiologist at Winthrop University Hospital, Mineola, NY, and partner at Neurologic Surgery PC. He was reimbursed by the grant for case enrollment. E. Moquete: NINDS ARUBA grant UO1 NS51566; study leader for coordination of data submission from the 39 sites in the trial. C. Moy: NINDS project scientist. E. Vicaut: ARUBA reimbursement for patient enrollment at Lariboisière, Paris. A. Moskowitz: NINDS ARUBA grant UO1 NS51566 UO1 NS51566, principal investigator of the Statistical Coordinating Center. K. Harkness: salaried neurologist in Sheffield UK, reimbursed from the grant for case enrollment. C. Cordonnier: salaried chief of university Neurology in Lille France, reimbursed from the grant for case enrollment. A. Biondi: salaried chief of university interventional neuroradiology in Besançon, France, reimbursed from the grant for case enrollment. E. Houdart: salary as interventional radiologist at Lariboisière, Paris, and interventional neuroradiologists at the European Coordinating Center, reimbursed from the grant for case enrollment. J. Berkefeld: salaried chief of university interventional neuroradiology in Frankfurt Germany, reimbursed from the grant for case enrollment. C. Klijn, MD: Neurologist at the University Medical Center Utrecht, the Netherlands (after ARUBA relocated to Nijmegen), reimbursed from the grant for case enrollment. X. Barreau: salaried chief of university interventional neuroradiology in Bordeaux France, reimbursed from the grant for case enrollment. H. Kim; NINDS-funded investigator from other grants, reimbursed from the grant for case enrollment at her center at University of California at San Francisco. A. Hartmann: salary as chair of Neurology Frankfurt-Oder and recipient of grant funds for reimbursement for patient enrollment. Go to Neurology.org for full disclosures.
Study Funding
Funded internationally by the US NIH/NINDS via cooperative agreements U01NS051483 (Clinical Coordinating Center; J.P. Mohr, principal investigator) and U01 NS051566 (Data Coordinating Center; A.J. Moskowitz, principal investigator). Gift support was also provided after cessation of NINDS funding from the Richard & Jenny Levine Foundation and the Vital Projects Fund.
Authors
Author Contributions
J.P. Mohr: principal investigator and director of the Clinical Coordinating Center, Columbia University; study concept and design; principal author of the manuscript; corresponding author. J.R. Overbey: associate of principal statistician Michael Parides, analysis and interpretation, critical revisions of the manuscript for intellectual content. R. von Kummer, M.A. Stefani, and R. Libman,: acquisition of data, critical revision of the manuscript for important intellectual content. C. Stapf: drafting/revising the manuscript, accepts responsibility for conduct of research and will give final approval, acquisition of data, obtaining funding. M.K. Parides: study concept and design, analysis and interpretation, statistical analysis, and critical revision of the manuscript for important intellectual content. J. Pile-Spellman: study concept and design, acquisition of data, critical revision of the manuscript for important intellectual content. E. Moquete: study concept and design, study coordinator, management of submitted data, critical revision of the manuscript for important intellectual content. C.S. Moy: study concept and design; study oversight, critical revision of the manuscript for important intellectual content. E. Vicaut: study concept and design, coinvestigator for the Aruba European Coordinating Center, analysis and interpretation, critical revision of the manuscript for important intellectual content. A.J. Moskowitz: study concept and design, coauthor of the manuscript, analysis and interpretation of data, critical revision of the manuscript for important intellectual content. K. Harkness, C. Cordonnier, A. Biondi, and E. Houdart: acquisition of data, critical revision of the manuscript for important intellectual content. J. Berkefeld: acquisition of data. C.J.M. Klijn: acquisition of data, critical revision of the manuscript for important intellectual content. X. Barreau: acquisition of data, review and approval of the manuscript for intellectual content. H. Kim: acquisition of data, critical revision of the manuscript for important intellectual content. A Hartmann: study concept and design, data acquisition for cases from Frankfurt-Oder and Charité Berlin, critical revision of manuscript for important intellectual content.
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