Treatment of Brain AVMs (TOBAS) Study

NCT02098252 | Recruiting

• 1 other identifier: 13.315
• Study Type: interventional
• Target: 1,000
• Locations: 6 countries
• Sites: 30

Brief Summary

The objectives of this study and registry are to offer the best management possible for patients with brain arteriovenous malformations (AVMs) (ruptured or unruptured) in terms of long-term outcomes, despite the presence of uncertainty. Management may include interventional therapy (with endovascular procedures, neurosurgery, or radiotherapy, alone or in combination) or conservative management. The trial has been designed to test a) whether medical management or interventional therapy will reduce the risk of death or debilitating stroke (due to hemorrhage or infarction) by an absolute magnitude of about 15% (over 10 years) for unruptured AVMs (from 30% to 15%); and, b) to test if endovascular treatment can improve the safety and efficacy of surgery or radiation therapy by at least 10% (80% to 90%). As for the nested trial on the role of embolization in the treatment of Brain AVMs by other means: the pre-surgical or pre-radiosurgery embolization of cerebral AVMs can decrease the number of treatment failures from 20% to 10%. In addition,embolization of cerebral AVMs can be accomplished with an acceptable risk, defined as permanent disabling neurological complications of 8%.

Conditions

Unruptured Brain Arteriovenous Malformation; Ruptured Brain Arteriovenous Malformation; Arteriovenous Malformations; AVM; BAVM

Keywords

brain arteriovenous malformation; Arteriovenous Malformations; AVM; BAVM; Stroke; Intracranial Hemorrhage; Congenital Abnormalities; Aneurysm; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases

Outcome Measures

Primary Outcomes (1)

• composite event of death from any cause or disabling stroke

  death or disabling stroke due to hemorrhage or infarction as revealed by imaging and resulting in mRS \>2.

  up to 10 years post-treatment (or randomization)

Secondary Outcomes (2)

• occurrence of any neurological event

  within 10 years following treatment (or after randomization)

• Permanent disabling peri-operative complications

  within 31 days post-treatment

Study Arms (2)

Interventional therapy

ACTIVE COMPARATOR

Interventional therapies include: neurosurgery (surgical resection when the lesion is considered by a multidisciplinary team to be safely 'operable'); radiation therapy (when the AVM is smaller than 3 cm, and considered to not be safely 'operable'); radiosurgery, alone or in combination, with or without endovascular procedure; curative embolization (when the lesion is considered curable by embolization). Patients with AVMs that the multidisciplinary team judges could potentially benefit from endovascular treatment prior to surgical resection or radiation therapy will then also be pre-randomly allocated to embolization or to no embolization.

Procedure: Neurosurgery; Radiation: Radiation therapy; Procedure: Embolization

Conservative management (medical management)

NO INTERVENTION

The conservative, or medical management arm, involves pharmacological therapy as deemed appropriate for medical symptoms as determined by the treating investigator. Should patients in the conservative management arm develop hemorrhage or infarction related to their AVM, they then potentially become candidates for interventional therapy.

Interventions

Neurosurgery PROCEDURE

Surgical resection to be used when the lesion is considered by a multidisciplinary team to be safely 'operable'.

Interventional therapy

Radiation therapy RADIATION

when the AVM is smaller than 3 cm, and considered to not be safely 'operable'.

Interventional therapy

Embolization PROCEDURE

Curative embolization, when the lesion is considered curable by embolization.

Interventional therapy

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with a brain AVM

You may not qualify if:

• Hemorrhagic presentation with mass effect requiring surgical management. In these cases, if a residual AVM is found after the initial surgery, the patient could then be a candidate for TOBAS.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Centre Hospitalier Régional et Universitaire de Brest: collaborator

Study Sites (30)

Mayo Clinic in Jacksonville FL

Jacksonville, Florida, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

RECRUITING

Hospital Geral de Fortaleza

Fortaleza, Brazil

RECRUITING

Universidade Federal de Sǎo Paulo

São Paulo, Brazil

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, Canada

RECRUITING

Klink, Ruby

Montreal, Quebec, H2L 4M1, Canada

RECRUITING

Instituto de Neurocirugia Dr. A. Asenjo

Santiago, Chile

RECRUITING

Universidad Autonoma de Bucaramanga

Bucaramanga, Colombia

RECRUITING

CHRU de Brest (Brest University Hospital)

Brest, Brittany Region, 29609, France

RECRUITING

Centre Hospit Régional Universitaire de Besançon

Besançon, 25030, France

RECRUITING

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, 33000, France

RECRUITING

Centre Hospitalier Universitaire de Caen

Caen, 14033, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, France

RECRUITING

CHU Dijon Bourgogne

Dijon, France

RECRUITING

Hôpital Bicêtre AP-HP

Le Kremlin-Bicêtre, 94270, France

RECRUITING

CHU Limoges

Limoges, 87042, France

RECRUITING

Centre Hospitalier Universitaire de Lyon

Lyon, 69002, France

RECRUITING

Assistance Publique - Hôpitaux de Marseille

Marseille, 13005, France

RECRUITING

Centre Hospitalier Universitaire de Montpellier

Montpellier, 34000, France

RECRUITING

Centre Hospitalier Régional Universitaire de Nancy

Nancy, 54035, France

RECRUITING

Centre Hospitalier Universitaire de Nantes

Nantes, 44093, France

RECRUITING

Hôpital Universitaire Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Fondation Ophtalmologique Rothschild

Paris, 75019, France

RECRUITING

Centre Hospitalier Sainte-Anne

Paris, 75674, France

RECRUITING

Centre Hospitalier Universitaire de Rennes

Rennes, 35033, France

RECRUITING

Centre Hospitalier Universitaire Hôpitaux de Rouen

Rouen, 76130, France

RECRUITING

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, 67200, France

RECRUITING

Centre Hospitalier Universitaire de Toulouse

Toulouse, 70034, France

RECRUITING

Centre Hospitalier Régional Universitaire de Tours

Tours, 37000, France

RECRUITING

Related Publications (26)

• Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet. 2002 Mar 9;359(9309):863-73. doi: 10.1016/S0140-6736(02)07946-1.

  PMID: 11897302 BACKGROUND

• Wedderburn CJ, van Beijnum J, Bhattacharya JJ, Counsell CE, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Al-Shahi Salman R; SIVMS Collaborators. Outcome after interventional or conservative management of unruptured brain arteriovenous malformations: a prospective, population-based cohort study. Lancet Neurol. 2008 Mar;7(3):223-30. doi: 10.1016/S1474-4422(08)70026-7. Epub 2008 Feb 1.

  PMID: 18243054 BACKGROUND

• Brown RD Jr, Wiebers DO, Torner JC, O'Fallon WM. Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population-based study of intracranial vascular malformations in Olmsted Country, Minnesota. J Neurosurg. 1996 Jul;85(1):29-32. doi: 10.3171/jns.1996.85.1.0029.

  PMID: 8683279 BACKGROUND

• Brown RD Jr, Wiebers DO, Forbes G, O'Fallon WM, Piepgras DG, Marsh WR, Maciunas RJ. The natural history of unruptured intracranial arteriovenous malformations. J Neurosurg. 1988 Mar;68(3):352-7. doi: 10.3171/jns.1988.68.3.0352.

  PMID: 3343606 BACKGROUND

• Wilkins RH. Natural history of intracranial vascular malformations: a review. Neurosurgery. 1985 Mar;16(3):421-30. doi: 10.1227/00006123-198503000-00026.

  PMID: 3885072 BACKGROUND

• da Costa L, Wallace MC, Ter Brugge KG, O'Kelly C, Willinsky RA, Tymianski M. The natural history and predictive features of hemorrhage from brain arteriovenous malformations. Stroke. 2009 Jan;40(1):100-5. doi: 10.1161/STROKEAHA.108.524678. Epub 2008 Nov 13.

  PMID: 19008469 BACKGROUND

• Gross BA, Du R. Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg. 2013 Feb;118(2):437-43. doi: 10.3171/2012.10.JNS121280. Epub 2012 Nov 30.

  PMID: 23198804 BACKGROUND

• Hernesniemi JA, Dashti R, Juvela S, Vaart K, Niemela M, Laakso A. Natural history of brain arteriovenous malformations: a long-term follow-up study of risk of hemorrhage in 238 patients. Neurosurgery. 2008 Nov;63(5):823-9; discussion 829-31. doi: 10.1227/01.NEU.0000330401.82582.5E.

  PMID: 19005371 BACKGROUND

• Hartmann A, Mast H, Mohr JP, Koennecke HC, Osipov A, Pile-Spellman J, Duong DH, Young WL. Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke. 1998 May;29(5):931-4. doi: 10.1161/01.str.29.5.931.

  PMID: 9596237 BACKGROUND

• Hartmann A, Mast H, Mohr JP, Pile-Spellman J, Connolly ES, Sciacca RR, Khaw A, Stapf C. Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations. Stroke. 2005 Nov;36(11):2431-5. doi: 10.1161/01.STR.0000185723.98111.75. Epub 2005 Oct 13.

  PMID: 16224095 BACKGROUND

• Hartmann A, Stapf C, Hofmeister C, Mohr JP, Sciacca RR, Stein BM, Faulstich A, Mast H. Determinants of neurological outcome after surgery for brain arteriovenous malformation. Stroke. 2000 Oct;31(10):2361-4. doi: 10.1161/01.str.31.10.2361.

  PMID: 11022064 BACKGROUND

• Cockroft KM, Chang KE, Lehman EB, Harbaugh RE. AVM Management Equipoise Survey: physician opinions regarding the management of brain arteriovenous malformations. J Neurointerv Surg. 2014 Dec;6(10):748-53. doi: 10.1136/neurintsurg-2013-011030. Epub 2013 Dec 6.

  PMID: 24319022 BACKGROUND

• Cockroft KM. Unruptured brain arteriovenous malformations should be treated conservatively: no. Stroke. 2007 Dec;38(12):3310-1. doi: 10.1161/STROKEAHA.107.504613. Epub 2007 Oct 25. No abstract available.

  PMID: 17962584 BACKGROUND

• Stapf C, Mohr JP. Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke. 2007 Dec;38(12):3308-9. doi: 10.1161/STROKEAHA.107.504605. Epub 2007 Oct 25. No abstract available.

  PMID: 17962585 BACKGROUND

• van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ. Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA. 2011 Nov 9;306(18):2011-9. doi: 10.1001/jama.2011.1632.

  PMID: 22068993 BACKGROUND

• Davies JM, Yanamadala V, Lawton MT. Comparative effectiveness of treatments for cerebral arteriovenous malformations: trends in nationwide outcomes from 2000 to 2009. Neurosurg Focus. 2012 Jul;33(1):E11. doi: 10.3171/2012.5.FOCUS12107.

  PMID: 22746228 BACKGROUND

• Morgan MK, Davidson AS, Koustais S, Simons M, Ritson EA. The failure of preoperative ethylene-vinyl alcohol copolymer embolization to improve outcomes in arteriovenous malformation management: case series. J Neurosurg. 2013 May;118(5):969-77. doi: 10.3171/2012.11.JNS112064. Epub 2013 Jan 25.

  PMID: 23350776 BACKGROUND

• Pierot L, Fiehler J, Cognard C, Soderman M, Spelle L. Will a randomized trial of unruptured brain arteriovenous malformations change our clinical practice? AJNR Am J Neuroradiol. 2014 Mar;35(3):416-7. doi: 10.3174/ajnr.A3867. Epub 2014 Jan 16. No abstract available.

  PMID: 24436345 BACKGROUND

• Raymond J; TEAM collaborative group. Reflections on the TEAM trial: why clinical care and research should be reconciled. Can J Neurol Sci. 2011 Mar;38(2):198-202. doi: 10.1017/s0317167100011343.

  PMID: 21320821 BACKGROUND

• Saatci I, Geyik S, Yavuz K, Cekirge HS. Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg. 2011 Jul;115(1):78-88. doi: 10.3171/2011.2.JNS09830. Epub 2011 Apr 8.

  PMID: 21476804 BACKGROUND

• Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986 Oct;65(4):476-83. doi: 10.3171/jns.1986.65.4.0476.

  PMID: 3760956 BACKGROUND

• Raymond J, Gentric JC, Magro E, Nico L, Bacchus E, Klink R, Cognard C, Januel AC, Sabatier JF, Iancu D, Weill A, Roy D, Bojanowski MW, Chaalala C, Barreau X, Jecko V, Papagiannaki C, Derrey S, Shotar E, Cornu P, Eker OF, Pelissou-Guyotat I, Piotin M, Aldea S, Beaujeux R, Proust F, Anxionnat R, Costalat V, Corre ML, Gauvrit JY, Morandi X, Brunel H, Roche PH, Graillon T, Chabert E, Herbreteau D, Desal H, Trystram D, Barbier C, Gaberel T, Nguyen TN, Viard G, Gevry G, Darsaut TE; TOBAS Collaborative Group; Collaborators in the TOBAS Collaborative Group. Endovascular treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial. J Neurosurg. 2022 Oct 28;138(5):1393-1402. doi: 10.3171/2022.9.JNS22987. Print 2023 May 1.

  PMID: 37132535 DERIVED

• Darsaut TE, Magro E, Bojanowski MW, Chaalala C, Nico L, Bacchus E, Klink R, Iancu D, Weill A, Roy D, Sabatier JF, Cognard C, Januel AC, Pelissou-Guyotat I, Eker O, Roche PH, Graillon T, Brunel H, Proust F, Beaujeux R, Aldea S, Piotin M, Cornu P, Shotar E, Gaberel T, Barbier C, Corre ML, Costalat V, Jecko V, Barreau X, Morandi X, Gauvrit JY, Derrey S, Papagiannaki C, Nguyen TN, Abdalkader M, Tawk RG, Huynh T, Viard G, Gevry G, Gentric JC, Raymond J; TOBAS Collaborative Group; List of participating TOBAS centers and physicians. Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial. J Neurosurg. 2022 Sep 9;138(4):891-899. doi: 10.3171/2022.7.JNS22813. Print 2023 Apr 1.

  PMID: 36087316 DERIVED

• Magro E, Gentric JC, Batista AL, Kotowski M, Chaalala C, Roberge D, Weill A, Stapf C, Roy D, Bojanowski MW, Darsaut TE, Klink R, Raymond J. The Treatment of Brain AVMs Study (TOBAS): an all-inclusive framework to integrate clinical care and research. J Neurosurg. 2018 Jun;128(6):1823-1829. doi: 10.3171/2017.2.JNS162751. Epub 2017 Sep 1.

  PMID: 28862547 DERIVED

• Magro E, Gentric JC, Darsaut TE, Batista AL, Chaalala C, Roberge D, Weill A, Roy D, Bojanowski MW, Raymond J. [Treatment of brain AVMS (TOBAS): A randomized controlled trial and registry]. Neurochirurgie. 2016 Aug;62(4):197-202. doi: 10.1016/j.neuchi.2015.12.008. Epub 2016 May 25. French.

  PMID: 27236732 DERIVED

• Darsaut TE, Magro E, Gentric JC, Batista AL, Chaalala C, Roberge D, Bojanowski MW, Weill A, Roy D, Raymond J. Treatment of Brain AVMs (TOBAS): study protocol for a pragmatic randomized controlled trial. Trials. 2015 Nov 4;16:497. doi: 10.1186/s13063-015-1019-0.

  PMID: 26530856 DERIVED

MeSH Terms

Conditions

Arteriovenous Malformations; Stroke; Intracranial Hemorrhages; Congenital Abnormalities; Aneurysm; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases

Interventions

Neurosurgical Procedures; Radiotherapy; Embolization, Therapeutic

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Therapeutics; Hemostatic Techniques; Therapeutic Occlusion

Study Officials

• Daniel Roy, MD

  CHUM-Montreal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Roy, MD

CONTACT

514-890-8000; daniel.roy.chum@ssss.gouv.qc.ca

Tim Darsaut, MD

CONTACT

780-407-1440; tdarsaut@ualberta.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2014
• First Posted: March 27, 2014
• Study Start: May 1, 2014
• Primary Completion (Estimated): January 1, 2035
• Study Completion (Estimated): January 1, 2036
• Last Updated: August 15, 2024

Record last verified: 2024-08

Locations

CA (2); FR (21); BR (2); CL (1); US (3); CO (1)