A Randomized Trial of Unruptured Brain AVMs (ARUBA)

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ClinicalTrials.gov Identifier: NCT00389181

Recruitment Status : Completed

First Posted : October 18, 2006

Last Update Posted : June 4, 2015

Sponsor:

Collaborator:

National Institute of Neurological Disorders and Stroke (NINDS)

Information provided by (Responsible Party):

Jay Preston Mohr, Columbia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Arteriovenous Malformations, Cerebral	Procedure: Interventional therapy Other: Medical management	Phase 3

Detailed Description:

Brain arteriovenous malformations (BAVMs) are an infrequent but important cause of stroke, particularly in a young population. Current invasive treatment strategies are varied and include endovascular procedures, neurosurgery, and radiotherapy. All of these treatments are administered on the assumption that they can be achieved at acceptably minor complication rates, decrease the risk of subsequent hemorrhage, and lead to better long-term outcomes.

Recent data from the literature comparing initial presentation and outcome for patients with ruptured and unruptured BAVMs have raised the possibility that such elective invasive treatment for unruptured BAVMs may yield worse outcomes than managing patients symptomatically with therapy. Unfortunately, no controlled clinical trials have yet been undertaken for management of unruptured BAVMs to address these concerns. Therefore, the goal of this randomized controlled trial is to determine if the long-term outcomes of patients who receive medical management for symptoms (e.g., headache, seizures) associated with an unruptured BAVM are superior to those who receive medical management and invasive therapy to eradicate the BAVM.

Participants will be randomly assigned to receive either symptomatic medical management alone or such management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy). Functional assessment will be carried out at the time of randomization, pre-intervention and 48-hour post-intervention, and for all participants at 1 month, and at 6 month intervals throughout the follow up period which will be a minimum of 5 years.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	226 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized Trial of Unruptured Brain Arteriovenous Malformations
Study Start Date :	October 2006
Actual Primary Completion Date :	June 2013
Actual Study Completion Date :	May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arteriovenous Malformations

Genetic and Rare Diseases Information Center resources: Intracranial Arteriovenous Malformation

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Medical management Patients with unruptured BAVMs will receive symptomatic medical management alone.	Other: Medical management 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.
Active Comparator: Interventional therapy Patients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).	Procedure: Interventional therapy 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. Other: Medical management 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.

Arm

Intervention/treatment

Experimental: Medical management

Patients with unruptured BAVMs will receive symptomatic medical management alone.

Other: Medical management

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.

Active Comparator: Interventional therapy

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

Procedure: Interventional therapy

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.

Other: Medical management

Outcome Measures

Primary Outcome Measures :

Difference of 5-year event rates between two arms [ Time Frame: 5 years ]
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.

Secondary Outcome Measures :

Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention [ Time Frame: 5 years ]
The hypothesis to be tested is that early intervention decreases the risk of death or clinical impairment at 5 years post-randomization. (Rankin Score >/= 2)

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
Patient has a diagnosed venous malformation
Patient has a diagnosed neurocutaneous syndrome such as cerebro-retinal angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or Wyburn-Mason syndrome
Patient has diagnosed BAVMs in context of moya-moya-type changes
Patient has diagnosed hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00389181

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Locations


United States, Arizona
Barrow Neurological Institute, 350 West Thomas Road
Phoenix, Arizona, United States, 85013
United States, California
Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd
Los Angeles, California, United States, 90027
University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza
Los Angeles, California, United States, 90095-1769
Kaiser Permanente (SF)
Redwood City, California, United States, 94063
University of California at San Francisco, 1001 Potrero Avenue- Rm 3C-38
San Francisco, California, United States, 94110
United States, Florida
University of Miami
Miami, Florida, United States, 33146
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700
Maywood, Illinois, United States, 60153-3304
United States, Iowa
University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,
Iowa City, Iowa, United States, 52242-1009
United States, Michigan
Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road
Southfield, Michigan, United States, 48075
United States, New Jersey
St. Joseph's Regional Medical Center
Paterson, New Jersey, United States, 07503
United States, New York
SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189
Brooklyn, New York, United States, 11203-2098
Mercy Hospital of Buffalo
Buffalo, New York, United States, 14220
Winthrop University Hospital
Mineola, New York, United States, 11501
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136
New York, New York, United States, 10029
New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St
New York, New York, United States, 10032
United States, Pennsylvania
John P. Murtha Neuroscience & Pain Institute,1450 Scapl Ave, Suite 120,
Johnstown,, Pennsylvania, United States, 15904
Thomas Jefferson Hospital for Neuroscience
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street
Austin, Texas, United States, 78701
University of Texas Medical School in Houston
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212
Charlottesville, Virginia, United States, 22908
Sentara Medical Group
Norfolk, Virginia, United States, 23502
United States, Wisconsin
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226-4874
Australia, Queensland
Wesley Medical Center
Auchenflower, Queensland, Australia, 4066
Australia, Victoria
Austin Health, University of Melbourne 300 Waterdale Rd,Heidelberg Heights
Melbourne, Victoria, Australia, 3081
Austria
Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck
Innsbruck, Austria
Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030
Wien, Austria
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Brazil
Canada, Ontario
Hamilton General Hospital .237 Barton Street East
Hamilton, Ontario, Canada, L8L 2X2
London Health Sciences Center
London, Ontario, Canada, N6A 5W9
Canada, Quebec
CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street
Montreal, Quebec, Canada, H2L 4M1
Finland
Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266
Helsinki, Finland, FI-00029 HUS
France
Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent
Brest cedex, France, 29609
CHU Henri Mondor, Service de Neuroradiologie
Creteil Cedex, France, 94010
Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU
Lille Cedex, France, 59037
Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré
Paris cedex 10, France, 75475
Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis
Paris, France, 75014
European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,
Paris, France
Germany
Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30
Berlin, Germany, 12200
Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74
Dresden, Germany, 01307
Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55
Essen, Germany, 45147
Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16
Frankfurt am Main, Germany, 60528
Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64
Freiburg, Germany, 79106
Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165
Halle, Germany, 06112
Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52
Hamburg, Germany, 20246
Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400
Heidelberg, Germany, 69120
Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15
Munich, Germany, 81377
Italy
Bellaria Hospital, Department of Neurosurgery
Bologna, Italy, 40139
Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60
Milano, Italy, 20131
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 1 10-744
Netherlands
Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1
Groningen, Netherlands, 9700
Utrecht University Hospital, Heidelberglaan 100, 3584 CX
Utrecht, Netherlands
Spain
Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat
Barcelona, Spain, 08907
Switzerland
Inselspital, Neurologische Klinik, 3010 Bern
Schweiz, Switzerland
United Kingdom
Frenchay Hospital, Neuroradiology Department
Bristol, United Kingdom, BS 16 1LE
Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road
Edinburgh, United Kingdom, EH4 2XU
Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street
Leeds, United Kingdom, LS1 3EX
Walton Centre for Neurology, Lower Lane Fazakerley
Liverpool, United Kingdom, L9 7LJ
Institute of Neurology, Box 6, The National Hospital, Queen Square
London, United Kingdom, WC12N 3BG
Department of Neurosurgery, Newcastle General Hospital, Westgate Road
Newcastle upon Tyne, United Kingdom, NE4 6BE
Imaging Directorate, Derriford Hospital
Plymouth, United Kingdom, PL6 8DH
Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood
Preston, United Kingdom, PR2 9HP
Department of Neurology, Hope Hospital
Salford, United Kingdom, M6 8HD
Department of Neurology, Royal Hallamshire Hospital, Glossop Road
Sheffield, United Kingdom, 810 2JF

Sponsors and Collaborators

Columbia University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators


Principal Investigator:	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

More Information

Additional Information:

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. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

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. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

Stapf C, Mohr JP. Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke. 2007 Dec;38(12):3308-9. Epub 2007 Oct 25.


Responsible Party:	Jay Preston Mohr, Daniel Sciarra Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier:	NCT00389181 History of Changes
Other Study ID Numbers:	AAAB6286 U01NS051566 ( U.S. NIH Grant/Contract ) U01NS051483 ( U.S. NIH Grant/Contract )
First Posted:	October 18, 2006 Key Record Dates
Last Update Posted:	June 4, 2015
Last Verified:	June 2015

Keywords provided by Jay Preston Mohr, Columbia University:


Unruptured brain arteriovenous malformation AVM BAVM Stroke Intracranial Hemorrhage

Additional relevant MeSH terms:


Congenital Abnormalities Arteriovenous Malformations Hemangioma Intracranial Arteriovenous Malformations Vascular Malformations Cardiovascular Abnormalities Cardiovascular Diseases Vascular Diseases Neoplasms, Vascular Tissue	Neoplasms by Histologic Type Neoplasms Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Central Nervous System Vascular Malformations Nervous System Malformations Intracranial Arterial Diseases

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