ARUBA – A Randomized Trial of Unruptured Brain AVMs

Rationale: Current invasive treatment for brain arteriovenous malformations (AVMs) is varied and includes endovascular procedures, neurosurgery, and radiotherapy alone and in combination, largely dependent on the decisions of the local clinical team. However, no controlled treatment data on invasive AVM therapy exist and recent data raise serious doubt about the treatment benefit for unruptured brain AVMs. We propose a randomized treatment trial testing the hypothesis that medical management improves long-term outcomes of patients with unruptured AVMs compared to invasive treatment.

Design: ARUBA is an international, multicenter, randomized, controlled, open, prospective clinical trial.

Sample size: 800 patients (1:1 random assignment).

Population studied: Patients aged ≥18 years, diagnosed with an unruptured brain AVM considered treatable by the local investigators.

Outcome measures: The primary outcome is the composite event of death from any cause or stroke (hemorrhage or infarction confirmed by imaging). Clinical outcome status will be measured by the Rankin Scale, NIHSS, EuroQual, and SF-36.

Interventions: Patients will be randomly assigned to invasive therapy (endovascular, surgical, and/or radiation therapy) versus medical management alone. Patients will be followed for a minimum of 5 years and a maximum of 7.5 years (mean 6.25 years) from randomization.

Statistical analysis: 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.

Trial status: Over 100 centers world-wide (62 US, 35 Europe, 3 Canada, 3 Australia) ready to participate. Patient enrollment will start in 2006.

Sponsor: NIH/NINDS.

Principal Investigator: J.P. Mohr, MD.

Principal Co-Investigator (Europe): C. Stapf, MD.

Website: www.arubastudy.org.

The presentation will provide details on both, study rationale and design.