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A Randomized Trial of Unruptured Brain AVMs (ARUBA)

Primary Purpose

Arteriovenous Malformations, Cerebral

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Interventional therapy

Medical management

About this trial

This is an interventional treatment trial for Arteriovenous Malformations, Cerebral focused on measuring Unruptured brain arteriovenous malformation, AVM, BAVM, Stroke, Intracranial Hemorrhage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

Barrow Neurological Institute, 350 West Thomas Road
Kaiser Permanente Los Angeles Medical Center,4867 Sunset Blvd
University of California at Los Angeles, UCLA School of Medicine, 710 Westwood Plaza
Kaiser Permanente (SF)
University of California at San Francisco, 1001 Potrero Avenue- Rm 3C-38
University of Miami
Rush University Medical Center
Loyola University Stritch School of Medicine, Department of Neurology, 2160 S 1st Ave, Bldg 105/2700
University of Iowa Hospitals, Department of Neurology, 200 Hawkins Drive ,
Michigan Head and Spine Institute, Providence Hospital and Medical Center, 16001 West Nine Mile Road
St. Joseph's Regional Medical Center
SUNY Downstate Medical Center, 451 Clarkson Avenue, Box 1189
Mercy Hospital of Buffalo
Winthrop University Hospital
Long Island Jewish Medical Center
Mount Sinai Hospital, One Gustave L. Levy Place, Department of Neurosurgery- Box 1136
New York Presbyterian Hospital, Columbia Campus, Neurological Institute, 710 W. 168th St
John P. Murtha Neuroscience & Pain Institute,1450 Scapl Ave, Suite 120,
Thomas Jefferson Hospital for Neuroscience
Brackenridge Hospital, Brain and Spine Center, 601 East 15th Street
University of Texas Medical School in Houston
University of Virginia School of Medicine, Department of Neurosurgery, P.O. Box 800212
Sentara Medical Group
Marshfield Clinic
Medical College of Wisconsin
Wesley Medical Center
Austin Health, University of Melbourne 300 Waterdale Rd,Heidelberg Heights
Universitätsklinik für Neurologie, Anichstrasse 35, 6020 Innsbruck
Rudolfstiftung, Neurochirurgie, Juchgasse 25, A-1030
Hospital de Clinicas de Porto Alegre
Hamilton General Hospital .237 Barton Street East
London Health Sciences Center
CHUM Notre Dame Hospital, Department of Radiology, 1560 Sherbrooke Street
Helsinki University Central Hospital, Dept. of Neurosurgery, Topeliuksenkatu 5, Helsinki, P.O. Box 266
Hôpital de la Cavale-Blanche, Service de Neurologie, Bd. Tanguy Pringent
CHU Henri Mondor, Service de Neuroradiologie
Centre Hospitalier Régional et Universitaire de Lille, Clinique de Neurochirurgie, Hopital Roger Salengro, CHRU
Hôpital Lariboisière, Service de Neuroradiologie, 2, Rue Ambroise Paré
Hôpital Sainte Anne, Service de Neurochirurgie, Centre Hospitalier Sainte Anne, 1, Rue Cabanis
European Coordinating Center: Dept. of Neurology, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris cedex 10,
Charité Campus Benjamin Franklin (CCBF), Neurologische Klinik, Hindenburgdamm 30
Uniklinikum Dresden, Neuroradiologie, Fetscherstr. 74
Universitätsklinikum Essen, Institut für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Hufelandstraße 55
Uniklinikum Frankfurt, Institut für Neuroradiologie, Schleusenweg 2-16
Uniklinik Freiburg, Neuroradiology-Neurocenter, Breisacher Str. 64
Berufsgenossenschaftliche Kliniken Bergmannstrost, Klinik für Neurochirurgie, Merseburger Str. 165
Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52
Universitätsklinik Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400
Klinikum Großhadern, LMU München, Neurologische Klinik und Poliklinik, Marchionistr. 15
Bellaria Hospital, Department of Neurosurgery
Servizio di Neuroradiologia, Ospedale San Raffaele, Via Olgettina 60
Seoul National University Hospital
Department of Neurosurgery, Universitair Medisch Centrum Groningen Hanzeplein 1
Utrecht University Hospital, Heidelberglaan 100, 3584 CX
Hospital Universitari de Bellvitge, Sección de Neuroradiologia, c/ Feixa Llarga s/n, L'Hospitalet de Llobregat
Inselspital, Neurologische Klinik, 3010 Bern
Frenchay Hospital, Neuroradiology Department
Western General Hospital, Bramwell Dott Building, Department of Clinical Neurosciences, Crewe Road
Consultant Neurologist, Department of Neurology, Leeds General Infirmary, Great George Street
Walton Centre for Neurology, Lower Lane Fazakerley
Institute of Neurology, Box 6, The National Hospital, Queen Square
Department of Neurosurgery, Newcastle General Hospital, Westgate Road
Imaging Directorate, Derriford Hospital
Neuroscience Department, Royal Preston Hospital, Sharoe Green Lane, Fulwood
Department of Neurology, Hope Hospital
Department of Neurology, Royal Hallamshire Hospital, Glossop Road

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Medical management

Interventional therapy

Arm Description

Patients with unruptured BAVMs will receive symptomatic medical management alone.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Full Information

NCT ID

NCT00389181

First Posted

October 16, 2006

Last Updated

June 2, 2015

Sponsor

Columbia University

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT00389181

Brief Title

A Randomized Trial of Unruptured Brain AVMs

Acronym

ARUBA

Official Title

A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

October 2006 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arteriovenous Malformations, Cerebral

Keywords

Unruptured brain arteriovenous malformation, AVM, BAVM, Stroke, Intracranial Hemorrhage

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

226 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Medical management

Arm Type

Experimental

Arm Description

Patients with unruptured BAVMs will receive symptomatic medical management alone.

Arm Title

Interventional therapy

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

Interventional therapy

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Medical management

Intervention Description

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.

Primary Outcome Measure Information:

Title

Difference of 5-year event rates between two arms

Description

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.

Time Frame

5 years

Secondary Outcome Measure Information:

Title

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

Description

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)

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials: