A Randomized Trial of Unruptured Brain AVMs (ARUBA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jay Preston Mohr, Columbia University
ClinicalTrials.gov Identifier:
NCT00389181
First received: October 16, 2006
Last updated: April 22, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Unruptured Brain Arteriovenous Malformation
Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Composite event of death from any cause or symptomatic stroke (hemorrhage or infarction confirmed by imaging) [ Time Frame: from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Risk of death or clinical impairment (Rankin Score >/= 2) at 5 years post-randomization [ Time Frame: from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: October 2006
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1

Symptomatic medical management alone:

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: 2

Symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy):

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.

Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination]

All interventional procedures are standard of care for the treatment of AVMs. They are not experimental.

Endovascular procedures involve specially designed catheters/tubes position in the small arteries feeding blood to the AVM. The tubes are inserted into an artery in the groin and threaded up through the artery into the brain. Once positioned, the physician injects a special material that changes from liquid to solid very quickly. Once it solidifies, it blocks the artery that is feeding blood to the AVM.

Neurosurgery involves the opening of a portion of the skull and the brain's outer lining to get access to the AVM.

Radiosurgery involves high energy radiation (like X-rays) carefully targeted at the brain AVM to shrink it and, in the best results, eventually eliminate the artery-to-vein links and the risk of bleeding. The effect often takes one to two years to occur.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have unruptured BAVM diagnosed by MRI/MRA and/or angiogram
  • Patient must be 18 years of age or older

Exclusion Criteria:

  • Patient has evidence of recent or prior BAVM hemorrhage
  • Patient has received prior BAVM therapy (endovascular, surgical, radiotherapy)
  • Patient has BAVM deemed untreatable by local investigator, or has concomitant vascular or brain disease that interferes with/or contradicts any invasive 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/nl) or coagulopathy (spontaneous or iatrogenic INR>1.5)
  • Patient is pregnant or lactating
  • Patient has known allergy against iodine contrast agents, multiple-foci BAVMs, or any form of arteriovenous or spinal fistulas
  • Patient has a diagnosed Vein of Galen type malformation, cavernous malformation, dural arteriovenous fistula, venous malformation, or 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, or hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389181

  Hide Study Locations
Locations
United States, Arizona
Barrow Neurological Institute, 350 West Thomas Road
Phoenix, Arizona, United States, 85013
United States, California
University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza
Los Angeles, California, United States, 90095-1769
Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd
Los Angeles, California, United States, 90027
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
European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,
Paris, France
Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis
Paris, France, 75014
Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré
Paris cedex 10, France, 75475
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
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:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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, U01NS051483
Study First Received: October 16, 2006
Last Updated: April 22, 2013
Health Authority: United States: Federal Government

Keywords provided by Columbia University:
unruptured brain arteriovenous malformation
AVM
BAVM
Stroke
Intracranial Hemorrhage

Additional relevant MeSH terms:
Congenital Abnormalities
Arteriovenous Malformations
Hemangioma
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Diseases
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 14, 2014