A Randomized Trial of Unruptured Brain AVMs

NCT ID: NCT00389181

Last Updated: 2015-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

226 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-31

Study Completion Date

2015-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Arteriovenous Malformations, Cerebral

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Medical management

Patients with unruptured BAVMs will receive symptomatic medical management alone.

Group Type EXPERIMENTAL

Medical management

Intervention Type 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

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

Group Type ACTIVE_COMPARATOR

Interventional therapy

Intervention Type 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.

Medical management

Intervention Type 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.

Interventions

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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.

Intervention Type PROCEDURE

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Patient has BAVM presenting with evidence of recent or prior hemorrhage
2. Patient has received prior BAVM therapy (endovascular, surgical, radiotherapy)
3. 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)
4. Patient has baseline Rankin ≥2
5. Patient has concomitant disease reducing life expectancy to less than 10 years
6. Patient has thrombocytopenia (\< 100,000/μL),
7. Patient has uncorrectable coagulopathy (INR\>1.5)
8. Patient is pregnant or lactating
9. Patient has known allergy against iodine contrast agents
10. Patient has multiple-foci BAVMs
11. Patient has any form of arteriovenous or spinal fistulas

Previous diagnosis of any of the following -
12. Patient has a diagnosed Vein of Galen type malformation
13. Patient has a diagnosed cavernous malformation
14. Patient has a diagnosed dural arteriovenous fistula
15. Patient has a diagnosed venous malformation
16. Patient has a diagnosed neurocutaneous syndrome such as cerebro-retinal angiomatosis (von Hippel-Lindau), encephalo-trigeminal syndrome (Sturge-Weber), or Wyburn-Mason syndrome
17. Patient has diagnosed BAVMs in context of moya-moya-type changes
18. Patient has diagnosed hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Jay Preston Mohr

Daniel Sciarra Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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J.P. Mohr, MS, MD

Role: PRINCIPAL_INVESTIGATOR

Stroke Center/The Neurological Institute, Columbia University

Alan J. Moskowitz, MD

Role: PRINCIPAL_INVESTIGATOR

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

Michael Parides, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Christian Stapf, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Coordinating Center, Europe

Eric Vicaut, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Coordinating Center, Europe, Co-PI

Claudia S. Moy, PhD

Role: PRINCIPAL_INVESTIGATOR

NINDS, Co-PI

Locations

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Barrow Neurological Institute, 350 West Thomas Road

Phoenix, Arizona, United States

Site Status

Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd

Los Angeles, California, United States

Site Status

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

Los Angeles, California, United States

Site Status

Kaiser Permanente (SF)

Redwood City, California, United States

Site Status

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

San Francisco, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

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

Maywood, Illinois, United States

Site Status

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

Iowa City, Iowa, United States

Site Status

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

Southfield, Michigan, United States

Site Status

St. Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189

Brooklyn, New York, United States

Site Status

Mercy Hospital of Buffalo

Buffalo, New York, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

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

New York, New York, United States

Site Status

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

New York, New York, United States

Site Status

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

Johnstown, Pennsylvania, United States

Site Status

Thomas Jefferson Hospital for Neuroscience

Philadelphia, Pennsylvania, United States

Site Status

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

Austin, Texas, United States

Site Status

University of Texas Medical School in Houston

Houston, Texas, United States

Site Status

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

Charlottesville, Virginia, United States

Site Status

Sentara Medical Group

Norfolk, Virginia, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Wesley Medical Center

Auchenflower, Queensland, Australia

Site Status

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

Melbourne, Victoria, Australia

Site Status

Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck

Innsbruck, , Austria

Site Status

Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030

Vienna, , Austria

Site Status

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Site Status

Hamilton General Hospital .237 Barton Street East

Hamilton, Ontario, Canada

Site Status

London Health Sciences Center

London, Ontario, Canada

Site Status

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

Montreal, Quebec, Canada

Site Status

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

Helsinki, , Finland

Site Status

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

Brest, , France

Site Status

CHU Henri Mondor, Service de Neuroradiologie

Créteil, , France

Site Status

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

Lille, , France

Site Status

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

Paris, , France

Site Status

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

Paris, , France

Site Status

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

Paris, , France

Site Status

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

Berlin, , Germany

Site Status

Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74

Dresden, , Germany

Site Status

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

Essen, , Germany

Site Status

Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16

Frankfurt am Main, , Germany

Site Status

Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64

Freiburg im Breisgau, , Germany

Site Status

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

Halle, , Germany

Site Status

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

Hamburg, , Germany

Site Status

Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400

Heidelberg, , Germany

Site Status

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

Munich, , Germany

Site Status

Bellaria Hospital, Department of Neurosurgery

Bologna, , Italy

Site Status

Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60

Milan, , Italy

Site Status

Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1

Groningen, , Netherlands

Site Status

Utrecht University Hospital, Heidelberglaan 100, 3584 CX

Utrecht, , Netherlands

Site Status

Seoul National University Hospital

Seoul, Seoul, South Korea

Site Status

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

Barcelona, , Spain

Site Status

Inselspital, Neurologische Klinik, 3010 Bern

Schweiz, , Switzerland

Site Status

Frenchay Hospital, Neuroradiology Department

Bristol, , United Kingdom

Site Status

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

Edinburgh, , United Kingdom

Site Status

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

Leeds, , United Kingdom

Site Status

Walton Centre for Neurology, Lower Lane Fazakerley

Liverpool, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

Department of Neurosurgery, Newcastle General Hospital, Westgate Road

Newcastle upon Tyne, , United Kingdom

Site Status

Imaging Directorate, Derriford Hospital

Plymouth, , United Kingdom

Site Status

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

Preston, , United Kingdom

Site Status

Department of Neurology, Hope Hospital

Salford, , United Kingdom

Site Status

Department of Neurology, Royal Hallamshire Hospital, Glossop Road

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Austria Brazil Canada Finland France Germany Italy Netherlands South Korea Spain Switzerland United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 16415679 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32562682 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28878048 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24268105 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19953376 (View on PubMed)

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.

Reference Type DERIVED
PMID: 17962585 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.arubastudy.org

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.

Other Identifiers

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U01NS051566

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01NS051483

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAB6286

Identifier Type: -

Identifier Source: org_study_id

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