MedPath

A Randomized Trial of Unruptured Brain AVMs

Phase 3
Completed
Conditions
Arteriovenous Malformations, Cerebral
Interventions
Procedure: Interventional therapy
Other: Medical management
Registration Number
NCT00389181
Lead Sponsor
Columbia University
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
226
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Interventional therapyInterventional therapyPatients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).
Interventional therapyMedical managementPatients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).
Medical managementMedical managementPatients with unruptured BAVMs will receive symptomatic medical management alone.
Primary Outcome Measures
NameTimeMethod
Difference of 5-year event rates between two arms5 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
NameTimeMethod
Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention5 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)

Trial Locations

Locations (66)

Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck

🇦🇹

Innsbruck, Austria

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

🇦🇺

Melbourne, Victoria, Australia

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

🇫🇮

Helsinki, Finland

Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1

🇳🇱

Groningen, Netherlands

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

🇺🇸

Austin, Texas, United States

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

🇺🇸

Johnstown,, Pennsylvania, United States

Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60

🇮🇹

Milano, Italy

Department of Neurosurgery, Newcastle General Hospital, Westgate Road

🇬🇧

Newcastle upon Tyne, United Kingdom

Department of Neurology, Royal Hallamshire Hospital, Glossop Road

🇬🇧

Sheffield, United Kingdom

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

🇨🇦

Montreal, Quebec, Canada

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

🇫🇷

Paris, France

Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16

🇩🇪

Frankfurt am Main, Germany

Mercy Hospital of Buffalo

🇺🇸

Buffalo, New York, United States

Sentara Medical Group

🇺🇸

Norfolk, Virginia, United States

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Imaging Directorate, Derriford Hospital

🇬🇧

Plymouth, United Kingdom

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

🇬🇧

Preston, United Kingdom

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

🇪🇸

Barcelona, Spain

Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74

🇩🇪

Dresden, Germany

Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64

🇩🇪

Freiburg, Germany

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

🇺🇸

Charlottesville, Virginia, United States

Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030

🇦🇹

Wien, Austria

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

🇫🇷

Brest cedex, France

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

🇬🇧

Edinburgh, United Kingdom

SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189

🇺🇸

Brooklyn, New York, United States

Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400

🇩🇪

Heidelberg, Germany

London Health Sciences Center

🇨🇦

London, Ontario, Canada

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

🇺🇸

New York, New York, United States

Inselspital, Neurologische Klinik, 3010 Bern

🇨🇭

Schweiz, Switzerland

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

🇬🇧

Leeds, United Kingdom

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

🇩🇪

Munich, Germany

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Winthrop University Hospital

🇺🇸

Mineola, New York, United States

Long Island Jewish Medical Center

🇺🇸

New Hyde Park, New York, United States

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

🇫🇷

Paris, France

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

🇺🇸

New York, New York, United States

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

🇩🇪

Essen, Germany

Utrecht University Hospital, Heidelberglaan 100, 3584 CX

🇳🇱

Utrecht, Netherlands

CHU Henri Mondor, Service de Neuroradiologie

🇫🇷

Creteil Cedex, France

Frenchay Hospital, Neuroradiology Department

🇬🇧

Bristol, United Kingdom

Walton Centre for Neurology, Lower Lane Fazakerley

🇬🇧

Liverpool, United Kingdom

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

🇩🇪

Berlin, Germany

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

🇩🇪

Halle, Germany

Department of Neurology, Hope Hospital

🇬🇧

Salford, United Kingdom

St. Joseph's Regional Medical Center

🇺🇸

Paterson, New Jersey, United States

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

🇺🇸

Iowa City, Iowa, United States

Wesley Medical Center

🇦🇺

Auchenflower, Queensland, Australia

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

🇫🇷

Lille Cedex, France

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

🇫🇷

Paris cedex 10, France

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

🇩🇪

Hamburg, Germany

Bellaria Hospital, Department of Neurosurgery

🇮🇹

Bologna, Italy

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

🇬🇧

London, United Kingdom

Barrow Neurological Institute, 350 West Thomas Road

🇺🇸

Phoenix, Arizona, United States

Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd

🇺🇸

Los Angeles, California, United States

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

🇺🇸

Los Angeles, California, United States

Kaiser Permanente (SF)

🇺🇸

Redwood City, California, United States

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

🇺🇸

San Francisco, California, United States

University of Miami

🇺🇸

Miami, Florida, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

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

🇺🇸

Maywood, Illinois, United States

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

🇺🇸

Southfield, Michigan, United States

Thomas Jefferson Hospital for Neuroscience

🇺🇸

Philadelphia, Pennsylvania, United States

University of Texas Medical School in Houston

🇺🇸

Houston, Texas, United States

Marshfield Clinic

🇺🇸

Marshfield, Wisconsin, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Hamilton General Hospital .237 Barton Street East

🇨🇦

Hamilton, Ontario, Canada

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