Recent evidence has indicated an uncertainty of the best means of management for unruptured brain arteriovenous malformations (BAVMs), whether by medical management or invasive treatment. A Randomized trial of Unruptured Brain AVMs (ARUBA) is proposed in a re-application, conducted by two independent but highly coordinated units, ARUBA-CLIN and ARUBA-STAT. Patients will be randomized to medical management or to invasive treatment (endovascular, neurosurgical, or radiosurgery, alone or in combination) and followed for a minimum of 5 years. The primary hypothesis is that medical management improves long-term outcomes of patients with unruptured BAVMs compared to invasive treatment for the composite event of death from any cause or stroke (hemorrhage or infarction confirmed by imaging) and disability as measured by the Rankin Scale. The primary null hypothesis is that there is no difference between medical management or invasive treatment for these outcomes. The null hypothesis will be tested against the alternative hypothesis that there is a difference between treatments with a two-sided 0.05 level log-rank test. With a plan to enroll 800 patients at over 80 clinical sites, the test will have 87.5% power to detect a risk reduction of 40% (hazard ratio of 0.60), and 80% power to detect a risk reduction of 36.5% (hazard ratio of 0.635). These hazard ratios correspond to an absolute decrease in 5-year event rates of 7.5% and 6.7% respectively for medical management, from an assumed 5-year event rate of 20% for invasive treatment. ARUBA-CLIN, the clinical arm of the trial, will coordinate the day-to-day conduct of the trial and interface with a European arm. It will handle pre-randomization inquiries and respond to clinical queries and policy issues arising during the trial. An Executive Committee of ARUBA-CLIN and ARUBA-STAT investigators and senior coordinators will meet frequently under tightly specified and controlled communication protocols to implement the needs of the trial. The ARUBA-CLIN document outlines the background and preliminary work leading to the proposal, definitions, inclusion-exclusion criteria and the clinical sites which will participate in patient enrollment. The data management and statistical component is laid out in detail in the accompanying ARUBA-STAT proposal. An accompanying Manual of Protocol, including data collection forms, provides details for the implementation of the trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01NS051483-05S1
Application #
8649251
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Janis, Scott
Project Start
2006-01-13
Project End
2014-07-31
Budget Start
2010-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$671,870
Indirect Cost
$173,986
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Mohr, J P; Yaghi, Shadi (2015) Management of unbled brain arteriovenous malformation study. Neurol Clin 33:347-59
Mohr, J P (2014) Results of ARUBA are applicable to most patients with nonruptured arteriovenous malformations. Stroke 45:1541-2
Mohr, J P; Parides, Michael K; Stapf, Christian et al. (2014) Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614-21
Mohr, J P; Moskowitz, Alan J; Parides, Michael et al. (2012) Hull down on the horizon: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial. Stroke 43:1744-5
Mohr, J P; Moskowitz, Alan J; Stapf, Christian et al. (2010) The ARUBA trial: current status, future hopes. Stroke 41:e537-40
Stapf, Christian (2010) The rationale behind ""A Randomized Trial of Unruptured Brain AVMs"" (ARUBA). Acta Neurochir Suppl 107:83-5
Stapf, Christian; Mohr, J P (2007) Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke 38:3308-9