A Randomized Trial of Unruptured Brain AVMs - Full Text View

Sponsor:	Columbia University
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00389181

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Resource links provided by NLM:

MedlinePlus related topics: Arteriovenous Malformations

U.S. FDA Resources

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 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: No Intervention symptomatic medical management alone
2: Active Comparator symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy)	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.

Arms

Assigned Interventions

1: No Intervention

symptomatic medical management alone

2: Active Comparator

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

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.

Contacts and Locations

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

Contacts

Contact: J. P. Mohr, MS, MD	212 305 8033	jpm10@columbia.edu
Contact: Alan J. Moskowitz, MD	212.569.9567	Alan.Moskowitz@MSSM.EDU

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Locations

United States, Alabama
University of South Alabama, Stroke Center, 2451 Fillingim Street, Suite 10I	Recruiting
Mobile, Alabama, United States, 36617-2238
Contact: Richard Zweifler, M.D. 251-470-5801 rzweifle@usouthal.edu
United States, Arizona
Barrow Neurological Institute, 350 West Thomas Road	Recruiting
Phoenix, Arizona, United States, 85013
Contact: Joseph Zabramski, M.D. 602-406-3465 joseph.zabramski@bnaneuro.net
United States, California
University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza	Recruiting
Los Angeles, California, United States, 90095-1769
Contact: Jeffrey L. Saver, M.D. 310-794-6379 jsaver@ucla.edu
University of California at San Francisco, 1001 Potrero Avenue- Rm 3C-38	Recruiting
San Francisco, California, United States, 94110
Contact: William Young, M.D. 415-206-8906 youngw@anesthesia.ucsf.edu
United States, Illinois
Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700	Recruiting
Maywood, Illinois, United States, 60153-3304
Contact: Jose Biller, M.D. 708-216-2438 jbiller@lumc.edu
United States, Iowa
University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,	Recruiting
Iowa City, Iowa, United States, 52242-1009
Contact: Harold P. Adams, Jr., M.D. 319-356-5796 harold-adams@uiowa.edu
United States, Massachusetts
Boston University School of Medicine, 715 Albany St., Robinson Building B-605	Recruiting
Boston, Massachusetts, United States, 02118-2526
Contact: Carlos S. Kase, M.D. 617-638-5102 cskase@bu.edu
United States, Michigan
Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road	Recruiting
Southfield, Michigan, United States, 48075
Contact: Richard D. Fessler, M.D. 877-784-3667 richard.fessler@providence-stjohnhealth.org
United States, New York
Clinical Coordinating Center: Stroke Center/The Neurological Institute, Columbia University, 710 West 168th Street	Recruiting
New York, New York, United States, 10032
Contact: J. P. Mohr, MS, MD 212-305-8033 jpm10@columbia.edu
Data Coordinating Center: International Center for Health Outcomes and Innovation Research, Department of Health Policy, Mount Sinai School of Medicine 1425 Madison Ave, 2nd Fl	Recruiting
New York, New York, United States, 10029
Contact: Alan J. Moskowitz, MD 212-659-9567 Alan.Moskowitz@MSSM.EDU
Contact: Ellen Moquete, RN 212 659 9651 ellen.moquete@mountsinai.org
Long Island College Hospital, 339 Hicks Street	Recruiting
Brooklyn, New York, United States, 11201
Contact: Toby Gropen, M.D. 718-780-2897 tgropen@chpnet.org
SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189	Recruiting
Brooklyn, New York, United States, 11203-2098
Contact: Sundeep Mangla, M.D. 718-270-2111 smangla@downstate.edu
Rochester General Hospital 1425 Portland Avenue	Withdrawn
Rochester, New York, United States, 14621-3095
Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136	Recruiting
New York, New York, United States, 10029
Contact: Jennifer Frontera, MD 212-241-9512 Jennifer.frontera@mountsinai.org
New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St	Recruiting
New York, New York, United States, 10032
Contact: Clinton B. Wright, MD 212-305-1710 cbw7@columbia.edu
United States, North Carolina
Wake Forest University School of Medicine, Department of Neurology, Medical Center Boulevard	Recruiting
Winston Salem, North Carolina, United States, 27157-1029
Contact: John A. Wilson, M.D. 336-716-4020 jawilson@wfubmc.edu
Contact: Stephen Glazier, M.D. 336-716-9728 sglazier@wfubmc.edu
United States, Pennsylvania
University of Pittsburgh Medical Center, Health System Stroke Institute, 200 Lothrop Street- C-400 PUH	Recruiting
Pittsburgh, Pennsylvania, United States, 15213-2582
Contact: Lawrence Wechsler, M.D. 412-647-8080 wechslerlr@upmc.edu
United States, Texas
Baylor College of Medicine, Department of Neurosurgery, 1709 Dryden Rd. (BCM-650)	Recruiting
Houston, Texas, United States, 77030-3411
Contact: Peng Roc Chen, M.D. 713-798-4696 prchen@bcm.tmc.edu
Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street	Recruiting
Austin, Texas, United States, 78701
Contact: J. Neal Rutledge, M.D. 512-795-5100 nrutledge@austin.rr.com
Seton Medical Center, 1201 West 38th Street	Recruiting
Austin, Texas, United States, 78701
Contact: J. Neal Rutledge, M.D. 512-795-5100 nrutledge@austin.rr.com
United States, Virginia
University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212	Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Aaron S. Dumont, M.D. 434-924-2735 asd2f@virginia.edu
United States, Washington
Seattle Neuroscience Institute/Swedish Medical, 550 17th Avenue, Suite 500	Recruiting
Seattle, Washington, United States, 98122
Contact: Marc Mayberg, M.D. 206-320-2805 marc.mayberg@swedish.org
Austria
Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030	Recruiting
Wien, Austria
Contact: Günther Kleinpeter, MD 43 1 711 65 4301 guenther.kleinpeter@wienkav.at
Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck	Recruiting
Innsbruck, Austria
Contact: Erich Schmutzhard, MD +43 512 5042-3853 erich.schmutzhard@i-med.ac.at
Canada, Quebec
CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street	Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Daniel Roy, M.D. 514-890-8000 Daniel.roy.chum@ssss.gouv.qc.ca
Finland
Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266	Recruiting
Helsinki, Finland, FI-00029 HUS
Contact: Aki Laaskso, MD, PhD +358 9 471 87415 aki.laakso@hus.fi
Contact: Juha Hernesniemi, MD, PhD +358 9 471 87415
France
European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,	Recruiting
Paris, France
Contact: Christian Stapf, MD +33 1 4995 2597 christian.stapf@lrb.aphp.fr
Contact: Cecile Dert cecile.dert@lrb.aphp.fr
Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent	Recruiting
Brest cedex, France, 29609
Contact: Serge Timsit, MD +33 2 9834 7300 serge.timsit@chu-brest.fr
CHU Henri Mondor, Service de Neuroradiologie	Recruiting
Creteil Cedex, France, 94010
Contact: André Gaston, MD +33 1 4981 2641 andre.gaston@hmm.aphp.fr
Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU	Recruiting
Lille Cedex, France, 59037
Contact: Jean-Paul Lejeune, MD +33 3 2044 6615 jp-lejeune@chru-lille.fr
Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis	Recruiting
Paris, France, 75014
Contact: François Nataf, MD +33 1 4565 8232 f.nataf@ch-sainte-anne.fr
Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré	Recruiting
Paris cedex 10, France, 75475
Contact: Emmanuel Houdart, MD +33 1 4995 6135 emmanuel.houdart@lrb.aphp.fr
Germany
Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16	Recruiting
Frankfurt am Main, Germany, 60528
Contact: Joachim Berkefeld, MD +49 69 6301 5462 berkefeld@em.uni-frankfurt.de
Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74	Recruiting
Dresden, Germany, 01307
Contact: Rüdiger von Kummer, MD +49 351 458 2660 ruediger.vonkummer@uniklinikum-dresden.de
Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55	Recruiting
Essen, Germany, 45147
Contact: Isabel Wanke, MD +49 201 723-1509 isabel.wanke@uni-due.de
Contact: Michael Forsting, MD +49 201 723-1509
Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30	Recruiting
Berlin, Germany, 12200
Contact: Andreas Hartmann, MD +49 30 84452275 andreas.hartmann@charite.de
Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64	Recruiting
Freiburg, Germany, 79106
Contact: Martin Schumacher, MD +49 761 270 5180 martin.schumacher@uniklinik-freiburg.de
Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165	Recruiting
Halle, Germany, 06112
Contact: Hans Jörg Meisel, MD +49 345 132 7404 meisel@bergmannstrost.com
Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400	Recruiting
Heidelberg, Germany, 69120
Contact: Berk Orakcioglu, MD +49 6221 56 38922 berk.orakcioglu@med.uni-heidelberg.de
Contact: Andreas Unterberg, MD +49 6221 56 38922
Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15	Recruiting
Munich, Germany, 81377
Contact: Martin Dichgans, MD +49 89 7095 3670 martin.dichgans@med.uni-muenchen.de
Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52	Recruiting
Hamburg, Germany, 20246
Contact: Ulrich Grzyska, MD +49 40 42803 2746 grzyska@uke.uni-hamburg.de
Italy
Bellaria Hospital, Department of Neurosurgery	Recruiting
Bologna, Italy, 40139
Contact: Eugenio Pozzati, M.D. +39 051 6225111 eugenio.pozzati@ausl.bo.it
Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60	Recruiting
Milano, Italy, 20131
Contact: Giuseppe Scotti, MD +39 (02) 2643 2239 scotti.giuseppe@hsr.it
Netherlands
Utrecht University Hospital, Heidelberglaan 100, 3584 CX	Recruiting
Utrecht, Netherlands
Contact: H. Bart van der Worp + 31 30 2509111 h.b.vanderworp@umcutrecht.nl
Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1	Recruiting
Groningen, Netherlands, 9700
Contact: J.M.C. van Dijk, MD +31 050 361 6161 j.m.c.van.dijk@nchir.umcg.nl
Spain
Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat	Recruiting
Barcelona, Spain, 08907
Contact: Maria Angels De Miquel, MD +34 93 260 7536 mademiquel@csub.scs.es
Switzerland
Inselspital, Neurologische Klinik, 3010 Bern	Recruiting
Schweiz, Switzerland
Contact: Marcel Arnold, MD +41 31 632 3156 marcel.arnold@insel.ch
United Kingdom
Frenchay Hospital, Neuroradiology Department	Recruiting
Bristol, United Kingdom, BS 16 1LE
Contact: Andrew Molyneux, MD +44 117 975 3982 andrew.molyneux@nbt.nhs.uk
Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road	Recruiting
Edinburgh, United Kingdom, EH4 2XU
Contact: Rustam Al-Shahi Salman, MD +44 131 537 2915 rustam.al-shahi@ed.ac.uk
Walton Centre for Neurology, Lower Lane Fazakerley	Recruiting
Liverpool, United Kingdom, L9 7LJ
Contact: Mohsen , Javadpour, MD +44 151 5671 mohsen.javadpour@thewaltoncentre.uhs.uk
Department of Neurosurgery, Newcastle General Hospital, Westgate Road	Recruiting
Newcastle upon Tyne, United Kingdom, NE4 6BE
Contact: David Mendelow, MD +44 191-233-6161 ext 22160 a.d.mendelow@newcastle.ac.uk
Contact: Barbara Gregson +44 191 233 6161 ext 22175 barbara.gregson@ncl.ac.uk
Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street	Recruiting
Leeds, United Kingdom, LS1 3EX
Contact: Ahmad Hassan, MD +44 113 392 8132 ahmad.hassan@leedsth.nhs.uk
Contact: John Bamford, MD +44 113 392 8132
Imaging Directorate, Derriford Hospital	Recruiting
Plymouth, United Kingdom, PL6 8DH
Contact: William M. Adams, MD +44 175 251 7917 william.adams@phnt.swest.nhs.uk
Department of Neurology, Royal Hallamshire Hospital, Glossop Road	Recruiting
Sheffield, United Kingdom, 810 2JF
Contact: Kirsty Harkness, MD +44 114 271 3810 kirsty.harkness@sth.nhs.uk
Department of Neurology, Hope Hospital	Recruiting
Salford, United Kingdom, M6 8HD
Contact: Jane Wainwright, MD +44 161 206 4044 Jane.Wainwright@srft.nhs.uk
Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood	Recruiting
Preston, United Kingdom, PR2 9HP
Contact: Tufail Patankar, MD +44 1772 522532 tufail.patankar@lthtr.nhs.uk
Contact: Stephan Duberley +44 1772 524334 Stephen.Duberley@lthtr.nhs.uk
Institute of Neurology, Box 6, The National Hospital, Queen Square	Recruiting
London, United Kingdom, WC12N 3BG
Contact: Nicholas Losseff, MD 020 7829 8753 nicholas.losseff@uclh.nhs.uk

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:	Deborah Ascheim, MD	InCHOIR, Department of Health Policy, Mount Sinai School of Medicine, Co-PI
Principal Investigator:	Annetine Gelijns, PhD	InCHOIR, Department of Health Policy, Mount Sinai School of Medicine, Co-PI
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

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

Responsible Party:	Columbia University Medical Center ( JP Mohr MS MD Daniel Sciarra Professor of Neurology Neurological Insitute )
Study ID Numbers:	U01NS051483, U01NS051566
Study First Received:	October 16, 2006
Last Updated:	October 28, 2009
ClinicalTrials.gov Identifier:	NCT00389181 History of Changes
Health Authority:	United States: Federal Government