Plain English Summary
Background and study aims:
Normally, blood from the heart moves from arteries to veins through a fine network of small blood vessels called a capillary bed. Here the nutrients from the blood are released into the brain tissue and the pressure of the blood flow reduces before it enters the veins on its journey back to the heart. Arteriovenous malformations or AVMs of the brain are abnormal tangles of arteries and veins which usually date back to birth but can also result from head injury. In an AVM the arteries and veins are connected directly without a capillary bed, exposing the thin walled veins to high pressures which puts them at risk for rupturing and bleeding into the brain. The aim of this study is to find better ways of caring for people who have been discovered to have an AVM in the brain that has never bled (unruptured). We want to find out whether it is better to leave the AVM alone and simply treat the symptoms (medical management), as it has never bled, or to eliminate the AVM using one of several available techniques, including surgery, catheter embolization or radiation treatment. Although both medical management and interventional treatment have been used before to treat AVMs, they never have been compared to see which works best. The risk of having an AVM of the brain is that it could rupture and bleed, possibly injuring the brain and causing symptoms of stroke. Removing or closing up an AVM by means of surgery, radiation treatment or interventional treatment can also injure brain tissue and cause a stroke. Currently whether do not know whether there is less chance of brain injury when an unbled AVM is eliminated or is left alone.
Who can participate?
Adults aged 18 and over with an unruptured AVM
What does the study involve?
Patients are randomly allocated into two groups: one group undergoes AVM elimination and the other group does not. Patients in the AVM elimination group receive interventional treatment, either surgery, radiation treatment, or some combination of treatments, chosen by their doctor. Patients in both groups are followed up for between 5 and 7.5 years depending on how long it takes to enroll the 800 patients needed for the study. Patients are seen every 6 months for the first two years, and at least every year after that until the end of the study.
What are the possible benefits and risks of participating?
The treatment risks are the same as they would be if you received any of the approved treatments outside of the study.
Where is the study run from?
100 different institutions in North America, Europe, Australia and South America
When is the study starting and how long is it expected to run for?
August 2006 to March 2014
Who is funding the study?
The National Institute of Health and the National Institute of Neurological Disorders and Stroke (USA)
Who is the main contact?
Prof. Jay Preston Mohr
jpm10@mail.cumc.columbia.edu
Trial website
Contact information
Type
Scientific
Primary contact
Prof J. P. Mohr
ORCID ID
Contact details
Stroke Center / The Neurological Institute
Columbia University
710 West 168th Street
New York
10032
United States of America
+1 (0)212 305 8033
jpm10@columbia.edu
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00389181
Protocol/serial number
1 U01 NS051483-01A1
Study information
Scientific title
A Randomised trial of Unruptured Brain Arteriovenous malformations
Acronym
ARUBA
Study hypothesis
The primary hypothesis of this trial is that medical management improves long-term outcomes of patients with unruptured Brain ArterioVenous Malformations (BAVM) compared to invasive therapy (with endovascular procedures, neurosurgery, or radiotherapy, alone or in combination).
Review of literature at http://www.ncbi.nlm.nih.gov/pubmed/16415679
Ethics approval
Columbia University Medical Center Institutional Review Board, 02/11/2005, IRB# AAAB6286
Study design
Randomised open parallel-group international multicenter trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Unruptured brain arteriovenous malformation
Intervention
All 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. Those allocated to the invasive treatment arm will also receive endovascular attempts at occlusion of the nidus and feeding vessels, compiling or microsurgery for feeding artery aneurysms, microsurgery for BAVM itself, and
radiosurgery, these alone or in various combinations and timings.
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
1. To determine whether medical management is superior to invasive therapy for preventing the composite outcome of death from any cause or stroke (hemorrhage or infarction confirmed by imaging) in the treatment of unruptured BAVMs
2. If medical management is not superior to invasive therapy, to determine whether medical management is not inferior to invasive therapy for preventing the composite outcome of death from any cause or stroke (hemorrhage or infarction confirmed by imaging) in the treatment of unruptured BAVMs
Secondary outcome measures
To determine whether treatment of unruptured BAVMs by medical management decreases the risk of death or clinical impairment (Rankin Score more than or equal to two) at five years post-randomization compared to invasive therapy.
Overall trial start date
01/08/2006
Overall trial end date
01/03/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patient must have unruptured BAVM diagnosed by Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography (MRA) and/or angiogram
2. Patient must be 18 years of age or older
3. Patient must have signed informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
800
Participant 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 contraindicts any invasive therapy type (stenosis/occlusion of neck artery, prior brain surgery/radiation for other reasons)
4. Patient has baseline Rankin more than or equal to two
5. Patient has concomitant disease reducing life expectancy to less than ten years
6. Patient has thrombocytopenia (less than 100,000/nl)
7. Patient has coagulopathy (spontaneous or iatrogenic Inernational Normalised Ratio(INR) more than 1.5, Prothrombin Time (PT) more than 30)
8. Patient is pregnant, lactating, or plans to become pregnant
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
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)
Recruitment start date
01/08/2006
Recruitment end date
01/03/2014
Locations
Countries of recruitment
Australia, Brazil, Canada, Czech Republic, Finland, France, Germany, Italy, Lithuania, Netherlands, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States of America
Trial participating centre
Columbia University
New York
10032
United States of America
Sponsor information
Organisation
NIH - National Institute of Neurological Disorders and Stroke (USA)
Sponsor details
c/o Claudia S. Moy
Neuroscience Center
Room 2214
6001 Executive Blvd.
MSC9520
Bethesda MD
20892-9520
United States of America
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
National Institutes of Health
Alternative name(s)
NIH
Funding Body Type
government organisation
Funding Body Subtype
federal/national government
Location
United States of America
Funder name
National Institute of Neurological Disorders and Stroke: 1 U01 NS051483-01A1
Alternative name(s)
NINDS
Funding Body Type
government organisation
Funding Body Subtype
federal/national government
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 protocol in http://www.ncbi.nlm.nih.gov/pubmed/19953376
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/24268105
Publication citations
-
Protocol
Stapf C, The rationale behind "A Randomized Trial of Unruptured Brain AVMs" (ARUBA)., Acta Neurochir. Suppl., 2010, 107, 83-85, doi: 10.1007/978-3-211-99373-6_13.
-
Results
Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, Al-Shahi Salman R, Vicaut E, Young WL, Houdart E, Cordonnier C, Stefani MA, Hartmann A, von Kummer R, Biondi A, Berkefeld J, Klijn CJ, Harkness K, Libman R, Barreau X, Moskowitz AJ, , Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial., Lancet, 2014, 383, 9917, 614-621, doi: 10.1016/S0140-6736(13)62302-8.