ARUBA, a randomized trial of unruptured brain arteriovenous malformations, is a project formulated by the staff of the Doris & Stanley Tananbaum Stroke Center, Neurological Institute and the InCHOIR Clinical Trial Center, both of the Columbia University Medical Center .
Current treatment of brain arteriovenous malformations (BAVMs) is varied and includes endovascular procedures, neurosurgery, and radiotherapy. All of these treatments are administered on the assumption that they will decrease the risk of subsequent hemorrhage and lead to better long-term outcomes. The literature on the subject contains almost no reference to the outcome for natural history or treatment for unruptured BAVMs. Published reports typically have blended the two cohorts together as if they have the same outcome risk. Recent data from the literature, including that from Columbia University’s Neurological Institute, comparing initial presentation and outcome for those presenting ruptured or unruptured, have raised the possibility that interventional treatment in patients with unruptured BAVMs may be detrimental compared with natural history, but no definitive information exists on the patient population overall nor on the outcomes estimated by either the commonly-used Spetzler-Martin Scale or the Neurological Institute Hemorrhage Risk Profile.
The goal of the project is to test the null hypothesis that treatment, by means of interventional procedures, surgery, or radiotherapy offers no difference in the risk of death or symptomatic stroke, and no better functional outcome than does conservative management at five years from discovery of an unruptured brain arteriovenous malformation (BAVM).
Adult patients discovered with a BAVM not having bled, as documented by any of several imaging techniques (angiography not required if CT or MR satisfactorily demonstrate the lesion) and whose lesion appears feasible for treatment, will be asked to participate in the randomization process. The alternative hypothesis is that death or symptomatic stroke will differ by an absolute magnitude of at least 10% over 5 years for the non-interventional versus the interventional arms. A secondary hypothesis is that there will be no difference in functional outcome comparing the two arms as assessed by the Rankin scale and the European Quality of Life Scale will be used for outcome assessment. A 5-year period of follow-up for outcome is selected for comparison, based on this time frame within which most of the literature is represented.
To complement the information derived from assessing functional capacity, the trial formally measures the quality of life experienced by patients in both treatment arms. Quality of life is assessed in a longitudinal fashion using standard scales including a measure of general health status (SF-36) and a measure of patient preference (European Quality of Life Scale). The economic analysis, which is limited to U.S. centers, measures the direct cost of health care, including the cost of the initial assessment, all follow-up imaging studies and all hospitalizations for patients in both treatment arms. In addition to acute care facilities, the study captures the use of rehabilitative and long-term care facilities for stroke events in patients from both arms of the study.
To date more than one hundred major centers in the Americas, Europe and Australia have signed up to participate in this randomized trial.