Treatment of Brain AVMs (TOBAS): study protocol for a pragmatic randomized controlled trial

Abstract

BackgroundThe management of unruptured brain arteriovenous malformation (AVM) patients remains controversial. Furthermore, curative attempts to treat ruptured AVM patients have not been questioned so far, and there is a lack of prospective data on clinical results according to treatment modality. Endovascular treatment is often used aiming to improve the safety or efficacy of surgery or radiation therapy, but benefits have never been documented in a trial. A care trial context is needed to evaluate interventions at the same time they are practised.Methods/Trial designTOBAS is a pragmatic, prospective, multicenter, randomized, controlled trial and registry which offers a care trial context for brain AVM patients, including surgical resection, radiosurgery or endovascular embolization, alone or combined. The study includes two RCTs and a multimodality prospective registry. The objectives of the proposed study are to assess whether preventive interventions (surgery, embolization, radiation therapy, alone or combined), selected by the local treatment team and performed as locally practiced, randomly allocated and compared with conservative management, in unruptured brain AVM patients eligible for active or conservative management, can improve the proportion of patients having an independent outcome (modified Rankin Scale (mRS) < 3, as assessed by a standardized questionnaire administered by non-masked care personnel) at 10 years. All patients judged ineligible for randomized allocation are to be entered in a multimodal registry. The objective of a nested trial in patients with ruptured or unruptured AVMs to be treated by surgery or radiation therapy, is to assess whether pre-surgical or pre-radiation embolization, randomly allocated and compared with no embolization, can improve the proportion of patients with complete eradication of the AVM, as locally adjudicated, combined with a good clinical outcome (mRS < 3). The study will require up to 2000 patients in approximately 30 centers or more, followed for 10 years. TOBAS is registered at clinicaltrials.gov: NCT02098252 as of 25 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1019-0) contains supplementary material, which is available to authorized users.

Curative endovascular treatment for low-grade Spetzler-Martin brain arteriovenous malformations: a single-center prospective study

“…In the ARUBA study on unruptured bAVMs, the risk of treatment was higher than the risk of the natural history of the disease, especially for low-grade cases 1. This conclusion has since been challenged2; at present there is insufficient pragmatic evidence to provide clear guidelines 3. Moreover, when treatment has been started, the natural history of the bAVM is modified and an increased risk of hemorrhage is present, as compared with intact, unruptured bAVMs.…”

Measuring Clinical Uncertainty and Equipoise by Applying the Agreement Study Methodology to Patient Management Decisions

“…[23] Third, such studies can be a prelude to the design or conduct of such care trials. [11][12][13] When a reliability study is designed with a trial in view, it can provide empirical evidence of Freedman's notion of 'clinical equipoise', when 'an honest professional disagreement among expert clinicians about the preferred treatment' exists, [24] a result that may reassure clinicians, patients and ethics committees. In our view no such equipoise condition is necessary to proceed with a carefully designed trial when evidence regarding what to do is lacking.…”

Editorial: The ARUBA study: where do we go from here?

“…4 Finally, we draw encouragement from Drs. Elhammady and Heros' statement that "there has been a strong demand from government and health insurance agencies for evidence-based medicine and outcome measures.…”

“…We would like to take this opportunity to respond to the editorial and to clarify some important issues concerning the trial we propose. 4 Drs. Elhammady and Heros believe "that it would be difficult and impractical to conduct a proper RCT," and they would rather opt for "an intermediate, practical course of action" that could "improve the overall care of patients with unruptured AVMs."…”