A Randomized Trial of Unruptured Brain AVMs "ARUBA"

Completed

Phase 3 Results N/A

Trial Description

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.

Detailed Description

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.

Conditions

Interventions

  • Invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination] Procedure
    Intervention Desc: All interventional procedures are standard of care for the treatment of AVMs. They are not experimental. Endovascular procedures involve specially designed catheters/tubes position in the small arteries feeding blood to the AVM. The tubes are inserted into an artery in the groin and threaded up through the artery into the brain. Once positioned, the physician injects a special material that changes from liquid to solid very quickly. Once it solidifies, it blocks the artery that is feeding blood to the AVM. Neurosurgery involves the opening of a portion of the skull and the brain's outer lining to get access to the AVM. Radiosurgery involves high energy radiation (like X-rays) carefully targeted at the brain AVM to shrink it and, in the best results, eventually eliminate the artery-to-vein links and the risk of bleeding. The effect often takes one to two years to occur.
    ARM 1: Kind: Experimental
    Label: 2
    Description: 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.
  • Medical Management Other
    Other Names: Standard of Care
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Medical management
    Description: Patients with unruptured BAVMs will receive symptomatic medical management alone.
    ARM 2: Kind: Experimental
    Label: Interventional therapy
    Description: Patients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).
  • Interventional therapy Procedure
    Intervention Desc: All interventional procedures are standard of care for the treatment of AVMs. They are not experimental. 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.
    ARM 1: Kind: Experimental
    Label: Interventional therapy
    Description: Patients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

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. 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

Outcomes

Type Measure Time Frame Safety Issue
Primary The composite event of death from any cause or stroke (hemorrhage or infarction confirmed by imaging).
Secondary Risk of death or clinical impairment (Rankin Score >/= 2) at 5 years post-randomization. Clinical outcome status will be measured by the Rankin Scale, NIHSS, and EuroQual.
Primary Composite event of death from any cause or symptomatic stroke (hemorrhage or infarction confirmed by imaging) from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage Yes
Secondary Risk of death or clinical impairment (Rankin Score >/= 2) at 5 years post-randomization from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage Yes
Primary Difference of 5-year event rates between two arms 5 years Yes
Secondary Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention 5 years Yes

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