A Randomized Trial of Unruptured Brain AVMs

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.

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)