The ARUBA trial (A Randomized trial of Unruptured Brain Arteriovenous Malformations) is a seminal study that sought to determine the optimal management strategy for unruptured brain arteriovenous malformations (AVMs).
Design: ARUBA was a non-blinded, randomized, multicenter trial. It included 226 patients from 39 centers who had an unruptured brain AVM and were aged 18 years or older. Patients were randomly assigned to receive either medical management alone (the control group) or medical management plus interventional therapy (the intervention group), which included neurosurgery, embolization, or radiosurgery.
The ARUBA trial was a randomized, non-blinded study conducted across 39 clinical centers. It included 226 patients who were aged 18 years or older and had an unruptured brain arteriovenous malformation (AVM). Patients were randomly assigned to one of two groups:
- Medical management alone, which included any necessary treatment for symptoms and risk factors (such as anti-seizure medications or blood pressure control) but no active attempt to eradicate the AVM.
- Medical management plus interventional therapy, which included neurosurgery, endovascular procedures, radiosurgery, or a combination of these approaches to eliminate the AVM.
The primary outcome of the trial was the occurrence of death from any cause or a symptomatic stroke. The participants were followed up for a mean period of 33 months.
After a mean follow-up of 33 months, the trial found a significantly higher risk of death or stroke in the interventional therapy group compared to the medical management group. The primary outcome had occurred in 30.7% of patients in the interventional group and 10.1% of patients in the medical management group.
Specifically, the rate of stroke was 14.4% in the medical management group and 35.7% in the intervention group. The death rate was 1.4% in the medical management group and 4.2% in the intervention group.
The ARUBA trial concluded that, for patients with unruptured brain AVMs, medical management alone was associated with better outcomes than medical management plus interventional therapy over the period of the study.
This study has played a significant role in how AVMs are treated and has generated considerable discussion in the medical community. It’s important to note that the ARUBA trial’s findings should be considered alongside other factors, including the characteristics of the individual patient’s AVM, their overall health status, and the expertise and experience of the treating team.
Findings: The study was stopped early because an interim analysis found that the risk of the primary outcome was significantly lower in the medical management group than in the interventional therapy group. After a mean of 33 months of follow-up, the primary outcome had occurred in 10.1% of patients in the medical management group and 30.7% of those in the intervention group.
Conclusions: Based on these findings, the ARUBA trial concluded that medical management alone was superior to medical management plus interventional therapy for patients with unruptured brain AVMs, at least over the period of time the study covered.
1. Short follow-up period: The mean follow-up period of the ARUBA trial was approximately 33 months. Critics argue that this may not be long enough to adequately assess the risk of hemorrhage from an unruptured AVM over a patient’s lifetime or the long-term benefits of interventional therapy.
- High complication rate of interventional therapy: The trial reported a higher complication rate for interventional therapy than is typically reported in clinical practice. This has raised questions about whether the results are representative of outcomes when treatment is provided by experienced specialists in high-volume centers.
- Lack of representation of high-volume centers: Critics have pointed out that the trial may not have adequately represented high-volume centers with the most experience in treating AVMs. Inclusion of more of these centers may have resulted in lower complication rates from interventional therapy.
- Inclusion of all types of interventions: The trial included all types of interventional therapies (surgery, embolization, and radiosurgery) as a single group. However, these interventions can have different success rates and risk profiles, so their effects may not be comparable.
- Lack of patient-specific treatment planning: The trial did not account for individualized treatment plans based on the unique characteristics of each patient’s AVM. Some patients may benefit more from intervention, while others may be better suited to conservative management.
- Non-blinding of the trial: The trial was not blinded, meaning that patients and their doctors knew which treatment they were receiving. This could introduce bias in the reporting of outcomes.