For release: Thursday, May 9, 2013
Upon the recommendation of the ARUBA Data and Safety Monitoring Board, the NINDS has stopped enrollment of patient volunteers into the trial. Under the experimental conditions in this trial, the interim analysis of data collected to date shows that medical management is superior to intervention in patients with unruptured brain arteriovenous malformations (AVMs). The DSMB further recommended extended follow-up to determine whether the disparity in event rates will persist over time.
On May 10, 2013, the NINDS announced that A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) stopped enrollment. A pre-planned interim analysis was reviewed by the trial’s independent Data and Safety Monitoring Board on April 15, 2013. The data showed that after a mean follow-up of 33 months, the event rate in the intervention group was more than 3 times higher than in the medical management group. The DSMB’s decision was based upon the primary outcome in the study, time to stroke or death. This analysis included data from 224 participants enrolled at 39 sites world-wide.
ARUBA is a randomized, multi-center trial designed to evaluate whether symptomatic medical management improves long-term outcomes of patients with unruptured brain arteriovenous malformations compared to invasive treatment for the composite event of death from any cause or symptomatic stroke (hemorrhage or infarction confirmed by imaging); a secondary outcome is disability as measured by the Rankin Score. Invasive treatment could include endovascular procedures, neurosurgery, or radiotherapy alone or in combination. The intent was to randomize 400 participants and follow them for 5 to 10 years; however, because of the higher than expected event rate in the interventional arm compared with medical management, the DSMB has recommended stopping enrollment while continuing to follow all participants to determine whether the difference in stroke and death in the two arms changes over time. The study was not powered to detect differences in efficacy among the three interventional approaches. Detailed analysis of the data is ongoing and further results will be presented at the European Stroke Conference in London on May 31, 2013, with subsequent publication planned.
The ARUBA trial is conducted under the clinical leadership of J. P. Mohr, MD (Columbia University) and Christian Stapf, MD (Hôpital Lariboisière, Paris), and the data analytical and biostatistical leadership of Alan Moskowitz, MD and Michael Parides, PhD (Icahn School of Medicine at Mount Sinai). The study is supported by cooperative agreements from the NINDS. The DSMB is a committee of medical and statistical experts having no vested interest in the outcome of the trial. The committee is appointed by the NINDS and is charged with confidentially reviewing interim results of the trial.
Brain arteriovenous malformations (AVMs) are an infrequent but important cause of stroke, particularly in a young population. Current invasive treatment strategies are varied and include endovascular procedures, neurosurgery, and radiotherapy, alone or in combination. All of these treatments are administered on the assumption that they can be achieved at acceptably minor complication rates, decrease the risk of subsequent hemorrhage, and lead to better long-term outcomes.
Recent data from the literature comparing initial presentation and outcome for patients with ruptured and unruptured brain AVMs have raised the possibility that such elective invasive treatment for unruptured brain AVMs may yield worse outcomes than managing patients symptomatically with therapy. Unfortunately, no controlled clinical trials have previously been undertaken for management of unruptured brain AVMs to address these concerns. Therefore, the goal of ARUBA is to determine if the long-term outcomes of patients who receive medical management for symptoms (e.g., headache, seizures) associated with an unruptured BAVM are superior to those who receive medical management and invasive therapy to eradicate the BAVM.
Participants were randomly assigned to receive either symptomatic medical management alone or such management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy). Functional assessment is carried out at the time of randomization, pre-intervention and 48-hour post-intervention, and for all participants at 1 month, and at 6 month intervals throughout the follow up period, planned for a minimum of 5 years.
Phase: Phase 3
Please follow this link for trial eligibility information.
Study Design: Allocation: Randomized Endpoint
Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Study Locations: Multiple Locations Worldwide
Last Modified January 29, 2014