A Randomized Trial of Unruptured Brain AVMs

Arteriovenous Malformations, Cerebral Clinical Trial

— ARUBA  

Official title:

A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00389181
• Other study ID #: AAAB6286
• Secondary ID: U01NS051566U01NS
• Status: Completed
• Phase: Phase 3
• First received: October 16, 2006
• Last updated: June 2, 2015
• Start date: October 2006
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: May 2015
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Arteriovenous Malformations, Cerebral
• Congenital Abnormalities
• Hemangioma
• Intracranial Arteriovenous Malformations

Intervention

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.

Locations

Country	Name	City	State
Australia	Wesley Medical Center	Auchenflower	Queensland
Australia	Austin Health, University of Melbourne 300 Waterdale Rd,Heidelberg Heights	Melbourne	Victoria
Austria	Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck	Innsbruck
Austria	Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030	Wien
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Canada	Hamilton General Hospital .237 Barton Street East	Hamilton	Ontario
Canada	London Health Sciences Center	London	Ontario
Canada	CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street	Montreal	Quebec
Finland	Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266	Helsinki
France	Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent	Brest cedex
France	CHU Henri Mondor, Service de Neuroradiologie	Creteil Cedex
France	Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU	Lille Cedex
France	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	Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré	Paris cedex 10
Germany	Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30	Berlin
Germany	Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74	Dresden
Germany	Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55	Essen
Germany	Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16	Frankfurt am Main
Germany	Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64	Freiburg
Germany	Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165	Halle
Germany	Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52	Hamburg
Germany	Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400	Heidelberg
Germany	Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15	Munich
Italy	Bellaria Hospital, Department of Neurosurgery	Bologna
Italy	Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60	Milano
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1	Groningen
Netherlands	Utrecht University Hospital, Heidelberglaan 100, 3584 CX	Utrecht
Spain	Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat	Barcelona
Switzerland	Inselspital, Neurologische Klinik, 3010 Bern	Schweiz
United Kingdom	Frenchay Hospital, Neuroradiology Department	Bristol
United Kingdom	Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road	Edinburgh
United Kingdom	Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street	Leeds
United Kingdom	Walton Centre for Neurology, Lower Lane Fazakerley	Liverpool
United Kingdom	Institute of Neurology, Box 6, The National Hospital, Queen Square	London
United Kingdom	Department of Neurosurgery, Newcastle General Hospital, Westgate Road	Newcastle upon Tyne
United Kingdom	Imaging Directorate, Derriford Hospital	Plymouth
United Kingdom	Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood	Preston
United Kingdom	Department of Neurology, Hope Hospital	Salford
United Kingdom	Department of Neurology, Royal Hallamshire Hospital, Glossop Road	Sheffield
United States	Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street	Austin	Texas
United States	SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189	Brooklyn	New York
United States	Mercy Hospital of Buffalo	Buffalo	New York
United States	University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Texas Medical School in Houston	Houston	Texas
United States	University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,	Iowa City	Iowa
United States	John P. Murtha Neuroscience & Pain Institute,1450 Scapl Ave, Suite 120,	Johnstown,	Pennsylvania
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	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136	New York	New York
United States	New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St	New York	New York
United States	Sentara Medical Group	Norfolk	Virginia
United States	St. Joseph's Regional Medical Center	Paterson	New Jersey
United States	Thomas Jefferson Hospital for Neuroscience	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute, 350 West Thomas Road	Phoenix	Arizona
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	Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road	Southfield	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  Finland,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference of 5-year event rates between two arms	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.	5 years	Yes
Secondary	Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention	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)	5 years	Yes

External Links

•   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.