ARUBA: A Randomized Trial of Unruptured Brain AVMs

Sponsor

Columbia University (Other)

Overall Status

Completed

CT.gov ID

NCT00389181

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

226

Enrollment

Locations

Arms

103

Duration (Months)

3.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arteriovenous Malformations, Cerebral	Procedure: Interventional therapy Other: Medical management	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

226 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medical management Patients with unruptured BAVMs will receive symptomatic medical management alone.	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.
Active Comparator: Interventional therapy Patients with unruptured BAVMs will receive symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy).	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.

Arm

Intervention/Treatment

Experimental: Medical management

Patients with unruptured BAVMs will receive symptomatic medical management alone.

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.

Active Comparator: Interventional therapy

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

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

Outcome Measures

Primary Outcome Measures

Difference of 5-year event rates between two arms [5 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

Prevalence of the risk of death or clinical impairment at 5 years post-randomization with early intervention [5 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Previous diagnosis of any of the following -

Patient has a diagnosed Vein of Galen type malformation
Patient has a diagnosed cavernous malformation
Patient has a diagnosed dural arteriovenous fistula
Patient has a diagnosed venous malformation
Patient has a diagnosed 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
Patient has diagnosed hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute, 350 West Thomas Road	Phoenix	Arizona	United States	85013
2	Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd	Los Angeles	California	United States	90027
3	University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza	Los Angeles	California	United States	90095-1769
4	Kaiser Permanente (SF)	Redwood City	California	United States	94063
5	University of California at San Francisco, 1001 Potrero Avenue- Rm 3C-38	San Francisco	California	United States	94110
6	University of Miami	Miami	Florida	United States	33146
7	Rush University Medical Center	Chicago	Illinois	United States	60612
8	Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700	Maywood	Illinois	United States	60153-3304
9	University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,	Iowa City	Iowa	United States	52242-1009
10	Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road	Southfield	Michigan	United States	48075
11	St. Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
12	SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189	Brooklyn	New York	United States	11203-2098
13	Mercy Hospital of Buffalo	Buffalo	New York	United States	14220
14	Winthrop University Hospital	Mineola	New York	United States	11501
15	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
16	Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136	New York	New York	United States	10029
17	New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St	New York	New York	United States	10032
18	John P. Murtha Neuroscience & Pain Institute,1450 Scapl Ave, Suite 120,	Johnstown,	Pennsylvania	United States	15904
19	Thomas Jefferson Hospital for Neuroscience	Philadelphia	Pennsylvania	United States	19107
20	Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street	Austin	Texas	United States	78701
21	University of Texas Medical School in Houston	Houston	Texas	United States	77030
22	University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212	Charlottesville	Virginia	United States	22908
23	Sentara Medical Group	Norfolk	Virginia	United States	23502
24	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
25	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226-4874
26	Wesley Medical Center	Auchenflower	Queensland	Australia	4066
27	Austin Health, University of Melbourne 300 Waterdale Rd,Heidelberg Heights	Melbourne	Victoria	Australia	3081
28	Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck	Innsbruck		Austria
29	Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030	Wien		Austria
30	Hospital de Clinicas de Porto Alegre	Porto Alegre		Brazil
31	Hamilton General Hospital .237 Barton Street East	Hamilton	Ontario	Canada	L8L 2X2
32	London Health Sciences Center	London	Ontario	Canada	N6A 5W9
33	CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street	Montreal	Quebec	Canada	H2L 4M1
34	Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266	Helsinki		Finland	FI-00029 HUS
35	Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent	Brest cedex		France	29609
36	CHU Henri Mondor, Service de Neuroradiologie	Creteil Cedex		France	94010
37	Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU	Lille Cedex		France	59037
38	Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré	Paris cedex 10		France	75475
39	Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis	Paris		France	75014
40	European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,	Paris		France
41	Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30	Berlin		Germany	12200
42	Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74	Dresden		Germany	01307
43	Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55	Essen		Germany	45147
44	Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16	Frankfurt am Main		Germany	60528
45	Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64	Freiburg		Germany	79106
46	Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165	Halle		Germany	06112
47	Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52	Hamburg		Germany	20246
48	Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400	Heidelberg		Germany	69120
49	Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15	Munich		Germany	81377
50	Bellaria Hospital, Department of Neurosurgery	Bologna		Italy	40139
51	Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60	Milano		Italy	20131
52	Seoul National University Hospital	Seoul		Korea, Republic of	1 10-744
53	Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1	Groningen		Netherlands	9700
54	Utrecht University Hospital, Heidelberglaan 100, 3584 CX	Utrecht		Netherlands
55	Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat	Barcelona		Spain	08907
56	Inselspital, Neurologische Klinik, 3010 Bern	Schweiz		Switzerland
57	Frenchay Hospital, Neuroradiology Department	Bristol		United Kingdom	BS 16 1LE
58	Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road	Edinburgh		United Kingdom	EH4 2XU
59	Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street	Leeds		United Kingdom	LS1 3EX
60	Walton Centre for Neurology, Lower Lane Fazakerley	Liverpool		United Kingdom	L9 7LJ
61	Institute of Neurology, Box 6, The National Hospital, Queen Square	London		United Kingdom	WC12N 3BG
62	Department of Neurosurgery, Newcastle General Hospital, Westgate Road	Newcastle upon Tyne		United Kingdom	NE4 6BE
63	Imaging Directorate, Derriford Hospital	Plymouth		United Kingdom	PL6 8DH
64	Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood	Preston		United Kingdom	PR2 9HP
65	Department of Neurology, Hope Hospital	Salford		United Kingdom	M6 8HD
66	Department of Neurology, Royal Hallamshire Hospital, Glossop Road	Sheffield		United Kingdom	810 2JF

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: 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