A Randomized Trial of Unruptured Brain AVMs (ARUBA)

The purpose of this study is to determine if medical management is better than invasive therapy for improving the long-term outcome of patients with unruptured brain arteriovenous malformations.

Brain arteriovenous malformations (BAVMs) 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. 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 BAVMs have raised the possibility that such elective invasive treatment for unruptured BAVMs may yield worse outcomes than managing patients symptomatically with therapy. Unfortunately, no controlled clinical trials have yet been undertaken for management of unruptured BAVMs to address these concerns. Therefore, the goal of this randomized controlled trial 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 will be 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 will be 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 which will be a minimum of 5 years.

• No Intervention: 1

  Symptomatic medical management alone:

  Patients participating in the trial will receive the best medical management possible for the disorder being tested in the trial and for any general medical illnesses they are demonstrated to have. One important consideration in the medical management of patients in this trial is stroke risk factor reduction.

• Active Comparator: 2

  Symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy):

  A patient randomized to interventional therapy is expected to begin interventional therapy within 3 months following randomization. Interventional therapy consists of endovascular attempts at occlusion of the nidus and feeding vessels, coiling or microsurgery for feeding artery aneurysms, microsurgery for BAVM itself, and radiosurgery, these alone or in various combinations and timings.

  Intervention: Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination]

• Stapf C, Mohr JP, Choi JH, Hartmann A, Mast H. Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol. 2006 Feb;19(1):63-8. Review.
• Stapf C. The rationale behind "A Randomized Trial of Unruptured Brain AVMs" (ARUBA). Acta Neurochir Suppl. 2010;107:83-5.
• Stapf C, Mohr JP. Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke. 2007 Dec;38(12):3308-9. Epub 2007 Oct 25. No abstract available.

Inclusion Criteria:

• Patient must have unruptured BAVM diagnosed by MRI/MRA and/or angiogram
• Patient must be 18 years of age or older

Exclusion Criteria:

• Patient has evidence of recent or prior BAVM hemorrhage
• Patient has received prior BAVM therapy (endovascular, surgical, radiotherapy)
• Patient has BAVM deemed untreatable by local investigator, or has concomitant vascular or brain disease that interferes with/or contradicts any invasive therapy type (stenosis/occlusion of neck artery, prior brain surgery/radiation for other reasons)
• Patient has baseline Rankin ≥2
• Patient has concomitant disease reducing life expectancy to less than 10 years
• Patient has thrombocytopenia (< 100,000/nl) or coagulopathy (spontaneous or iatrogenic INR>1.5)
• Patient is pregnant or lactating
• Patient has known allergy against iodine contrast agents, multiple-foci BAVMs, or any form of arteriovenous or spinal fistulas
• Patient has a diagnosed Vein of Galen type malformation, cavernous malformation, dural arteriovenous fistula, venous malformation, or neurocutaneous syndrome such as cerebro-retinal angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or Wyburn-Mason syndrome
• Patient has diagnosed BAVMs in context of moya-moya-type changes, or hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)