A Randomized Trial of Unruptured Brain AVMs

NCT00389181 | Completed Phase 3 DMC

• 3 other identifiers: AAAB6286U01NS051566U01NS051483
• Study Type: interventional
• Target: 226
• Locations: 13 countries
• Sites: 64

Brief Summary

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.

Conditions

Arteriovenous Malformations, Cerebral

Keywords

Unruptured brain arteriovenous malformation; AVM; BAVM; Stroke; Intracranial Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Difference of 5-year event rates between two arms

  The hypothesis to be tested is that there is no difference between medical management and interventional therapy in the time to stroke or death from any cause.

  5 years

Secondary Outcomes (1)

• Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention

  5 years

Study Arms (2)

Medical management

EXPERIMENTAL

Patients with unruptured BAVMs will receive symptomatic medical management alone.

Other: Medical management

Interventional therapy

ACTIVE COMPARATOR

Patients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).

Procedure: Interventional therapy; Other: Medical management

Interventions

Interventional therapy PROCEDURE

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.

Interventional therapy

Medical management OTHER

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.

Interventional therapy; Medical management

Eligibility Criteria

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

You may qualify if:

• Patient must have unruptured BAVM diagnosed by MRI/MRA, CTA and/or angiogram
• Patient must be 18 years of age or older
• Patient must have signed Informed Consent, Release of Medical Information, and Health Insurance Portability and Accountability Act (HIPAA/U.S. only) Forms

You may not qualify if:

• Patient has BAVM presenting with evidence of recent or prior hemorrhage
• Patient has received prior BAVM therapy (endovascular, surgical, radiotherapy)
• Patient has BAVM deemed untreatable by local team, or has concomitant vascular or brain disease that interferes with/or contraindicates any interventional therapy type (stenosis/occlusion of neck artery, prior brain surgery/radiation for other reasons)
• Patient has baseline Rankin ≥2
• Patient has concomitant disease reducing life expectancy to less than 10 years
• Patient has thrombocytopenia (\< 100,000/μL),
• Patient has uncorrectable coagulopathy (INR\>1.5)
• Patient is pregnant or lactating
• Patient has known allergy against iodine contrast agents
• Patient has multiple-foci BAVMs
• Patient has any form of arteriovenous or spinal fistulas
• Previous diagnosis of any of the following -
• Patient has a diagnosed Vein of Galen type malformation
• Patient has a diagnosed cavernous malformation
• Patient has a diagnosed dural arteriovenous fistula

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (66)

Barrow Neurological Institute, 350 West Thomas Road

Phoenix, Arizona, 85013, United States

Location

Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd

Los Angeles, California, 90027, United States

Location

University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza

Los Angeles, California, 90095-1769, United States

Location

Kaiser Permanente (SF)

Redwood City, California, 94063, United States

Location

University of California at San Francisco, 1001 Potrero Avenue- Rm 3C-38

San Francisco, California, 94110, United States

Location

University of Miami

Miami, Florida, 33146, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700

Maywood, Illinois, 60153-3304, United States

Location

University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,

Iowa City, Iowa, 52242-1009, United States

Location

Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road

Southfield, Michigan, 48075, United States

Location

St. Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189

Brooklyn, New York, 11203-2098, United States

Location

Mercy Hospital of Buffalo

Buffalo, New York, 14220, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136

New York, New York, 10029, United States

Location

New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St

New York, New York, 10032, United States

Location

John P. Murtha Neuroscience & Pain Institute,1450 Scapl Ave, Suite 120,

Johnstown, Pennsylvania, 15904, United States

Location

Thomas Jefferson Hospital for Neuroscience

Philadelphia, Pennsylvania, 19107, United States

Location

Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street

Austin, Texas, 78701, United States

Location

University of Texas Medical School in Houston

Houston, Texas, 77030, United States

Location

University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212

Charlottesville, Virginia, 22908, United States

Location

Sentara Medical Group

Norfolk, Virginia, 23502, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-4874, United States

Location

Wesley Medical Center

Auchenflower, Queensland, 4066, Australia

Location

Austin Health, University of Melbourne 300 Waterdale Rd,Heidelberg Heights

Melbourne, Victoria, 3081, Australia

Location

Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck

Innsbruck, Austria

Location

Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030

Vienna, Austria

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil

Location

Hamilton General Hospital .237 Barton Street East

Hamilton, Ontario, L8L 2X2, Canada

Location

London Health Sciences Center

London, Ontario, N6A 5W9, Canada

Location

CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street

Montreal, Quebec, H2L 4M1, Canada

Location

Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266

Helsinki, FI-00029 HUS, Finland

Location

Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent

Brest, 29609, France

Location

CHU Henri Mondor, Service de Neuroradiologie

Créteil, 94010, France

Location

Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU

Lille, 59037, France

Location

Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis

Paris, 75014, France

Location

Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré

Paris, 75475, France

Location

European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,

Paris, France

Location

Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30

Berlin, 12200, Germany

Location

Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74

Dresden, 01307, Germany

Location

Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55

Essen, 45147, Germany

Location

Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16

Frankfurt am Main, 60528, Germany

Location

Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64

Freiburg im Breisgau, 79106, Germany

Location

Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165

Halle, 06112, Germany

Location

Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52

Hamburg, 20246, Germany

Location

Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400

Heidelberg, 69120, Germany

Location

Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15

Munich, 81377, Germany

Location

Bellaria Hospital, Department of Neurosurgery

Bologna, 40139, Italy

Location

Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60

Milan, 20131, Italy

Location

Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1

Groningen, 9700, Netherlands

Location

Utrecht University Hospital, Heidelberglaan 100, 3584 CX

Utrecht, Netherlands

Location

Seoul National University Hospital

Seoul, Seoul, 1 10-744, South Korea

Location

Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat

Barcelona, 08907, Spain

Location

Inselspital, Neurologische Klinik, 3010 Bern

Schweiz, Switzerland

Location

Frenchay Hospital, Neuroradiology Department

Bristol, BS 16 1LE, United Kingdom

Location

Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road

Edinburgh, EH4 2XU, United Kingdom

Location

Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street

Leeds, LS1 3EX, United Kingdom

Location

Walton Centre for Neurology, Lower Lane Fazakerley

Liverpool, L9 7LJ, United Kingdom

Location

Institute of Neurology, Box 6, The National Hospital, Queen Square

London, WC12N 3BG, United Kingdom

Location

Department of Neurosurgery, Newcastle General Hospital, Westgate Road

Newcastle upon Tyne, NE4 6BE, United Kingdom

Location

Imaging Directorate, Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood

Preston, PR2 9HP, United Kingdom

Location

Department of Neurology, Hope Hospital

Salford, M6 8HD, United Kingdom

Location

Department of Neurology, Royal Hallamshire Hospital, Glossop Road

Sheffield, 810 2JF, United Kingdom

Location

Related Publications (6)

• Stapf C, Mohr JP, Choi JH, Hartmann A, Mast H. Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol. 2006 Feb;19(1):63-8. doi: 10.1097/01.wco.0000200546.14668.78.

  PMID: 16415679 BACKGROUND

• Mohr JP, Overbey JR, Hartmann A, Kummer RV, Al-Shahi Salman R, Kim H, van der Worp HB, Parides MK, Stefani MA, Houdart E, Libman R, Pile-Spellman J, Harkness K, Cordonnier C, Moquete E, Biondi A, Klijn CJM, Stapf C, Moskowitz AJ; ARUBA co-investigators. Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial. Lancet Neurol. 2020 Jul;19(7):573-581. doi: 10.1016/S1474-4422(20)30181-2.

  PMID: 32562682 DERIVED

• Mohr JP, Overbey JR, von Kummer R, Stefani MA, Libman R, Stapf C, Parides MK, Pile-Spellman J, Moquete E, Moy CS, Vicaut E, Moskowitz AJ, Harkness K, Cordonnier C, Biondi A, Houdart E, Berkefeld J, Klijn CJM, Barreau X, Kim H, Hartmann A; International ARUBA Investigators. Functional impairments for outcomes in a randomized trial of unruptured brain AVMs. Neurology. 2017 Oct 3;89(14):1499-1506. doi: 10.1212/WNL.0000000000004532. Epub 2017 Sep 6.

  PMID: 28878048 DERIVED

• Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, Al-Shahi Salman R, Vicaut E, Young WL, Houdart E, Cordonnier C, Stefani MA, Hartmann A, von Kummer R, Biondi A, Berkefeld J, Klijn CJ, Harkness K, Libman R, Barreau X, Moskowitz AJ; international ARUBA investigators. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014 Feb 15;383(9917):614-21. doi: 10.1016/S0140-6736(13)62302-8. Epub 2013 Nov 20.

  PMID: 24268105 DERIVED

• Stapf C. The rationale behind "A Randomized Trial of Unruptured Brain AVMs" (ARUBA). Acta Neurochir Suppl. 2010;107:83-5. doi: 10.1007/978-3-211-99373-6_13.

  PMID: 19953376 DERIVED

• 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 DERIVED

Related Links

• An ARUBA web site has been developed to allow physicians to have access to up-to-date trial information. It will also be available to patients and their families.

MeSH Terms

Conditions

Intracranial Arteriovenous Malformations; Stroke; Intracranial Hemorrhages

Interventions

Practice Management, Medical

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Arteriovenous Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases; Intracranial Arterial Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Practice Management; Professional Practice; Organization and Administration; Health Services Administration

Study Officials

• J.P. Mohr, MS, MD

  Stroke Center/The Neurological Institute, Columbia University

  PRINCIPAL INVESTIGATOR

• Alan J. Moskowitz, MD

  InCHOIR, Department of Health Policy, Mount Sinai School of Medicine

  PRINCIPAL INVESTIGATOR

• Michael Parides, PhD

  InCHOIR, Department of Health Policy, Mount Sinai School of Medicine, Co-PI

  PRINCIPAL INVESTIGATOR

• Christian Stapf, MD

  Clinical Coordinating Center, Europe

  PRINCIPAL INVESTIGATOR

• Eric Vicaut, MD

  Clinical Coordinating Center, Europe, Co-PI

  PRINCIPAL INVESTIGATOR

• Claudia S. Moy, PhD

  NINDS, Co-PI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Daniel Sciarra Professor of Neurology

Study Record Dates

• First Submitted: October 16, 2006
• First Posted: October 18, 2006
• Study Start: October 1, 2006
• Primary Completion: June 1, 2013
• Study Completion: May 1, 2015
• Last Updated: June 4, 2015

Record last verified: 2015-06

Locations

GB (10); AU (2); US (25); CA (3); KR (1); BR (1); IT (2); NL (2); ES (1); DE (9); FR (6); FI (1); CH (1)