title: Treatment of Brain AVMs (TOBAS): study protocol for a pragmatic randomized controlled trial.
abstract: BACKGROUND
  The 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.
  TOBAS 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.
authors.affiliation: Department of Surgery, Division of Neurosurgery, University of Alberta Hospital, Mackenzie Health Sciences Center, Edmonton, AB, Canada. tdarsaut@ualberta.ca.
authors.forename: Tim E
authors.initials: TE
authors.lastname: Darsaut
authors.affiliation: Department of Surgery, Service of Neurosurgery, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Montreal, QC, Canada. elsa.magro@chu-brest.fr.|Service de Neurochirurgie, CHU Cavale Blanche, INSERM UMR 1101 LaTIM, Brest, France. elsa.magro@chu-brest.fr.
authors.forename: Elsa
authors.initials: E
authors.lastname: Magro
authors.affiliation: Department of Radiology, Service of Neuroradiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Interventional Neuroradiology (NRI), 1560 Sherbrooke East, Pavillion Simard, room Z12909, Montreal, QC, H2L 4 M1, Canada. jcgentric@gmail.com.|Service de Radiologie, CHU Cavale Blanche, EA 3878 GETBO, Brest, France. jcgentric@gmail.com.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Gentric
authors.affiliation: Department of Radiology, Service of Neuroradiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Interventional Neuroradiology (NRI), 1560 Sherbrooke East, Pavillion Simard, room Z12909, Montreal, QC, H2L 4 M1, Canada. batistaneuro@bol.com.br.
authors.forename: André Lima
authors.initials: AL
authors.lastname: Batista
authors.affiliation: Department of Surgery, Service of Neurosurgery, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Montreal, QC, Canada. chaalala@hotmail.com.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Chaalala
authors.affiliation: Department of Radio-Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Montreal, QC, Canada. drroberge@yahoo.com.
authors.forename: David
authors.initials: D
authors.lastname: Roberge
authors.affiliation: Department of Surgery, Service of Neurosurgery, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Montreal, QC, Canada. michel.bojanowski.chum@ssss.gouv.qc.ca.
authors.forename: Michel W
authors.initials: MW
authors.lastname: Bojanowski
authors.affiliation: Department of Radiology, Service of Neuroradiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Interventional Neuroradiology (NRI), 1560 Sherbrooke East, Pavillion Simard, room Z12909, Montreal, QC, H2L 4 M1, Canada. alain.weill.chum@ssss.gouv.qc.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Weill
authors.affiliation: Department of Radiology, Service of Neuroradiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Interventional Neuroradiology (NRI), 1560 Sherbrooke East, Pavillion Simard, room Z12909, Montreal, QC, H2L 4 M1, Canada. daniel.roy.chum@ssss.gouv.qc.ca.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roy
authors.affiliation: Department of Radiology, Service of Neuroradiology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Interventional Neuroradiology (NRI), 1560 Sherbrooke East, Pavillion Simard, room Z12909, Montreal, QC, H2L 4 M1, Canada. jean.raymond@umontreal.ca.
authors.forename: Jean
authors.initials: J
authors.lastname: Raymond
mesh_terms: D002985:Clinical Protocols; D004621:Embolization, Therapeutic / Q000009:adverse effects; D057510:Endovascular Procedures / Q000009:adverse effects; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000175:diagnosis / Q000601:surgery / Q000628:therapy*; D008866:Microsurgery / Q000009:adverse effects; D019635:Neurosurgical Procedures / Q000009:adverse effects; D018579:Patient Selection; D011446:Prospective Studies; D016634:Radiosurgery / Q000009:adverse effects; D012042:Registries; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome