A randomised trial of unruptured brain arteriovenous malformations
| ISRCTN | ISRCTN44013133 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44013133 |
| ClinicalTrials.gov number | NCT00389181 |
| Secondary identifying numbers | 1 U01 NS051483-01A1 |
- Submission date
- 25/06/2006
- Registration date
- 11/09/2006
- Last edited
- 22/06/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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
Contact information
Scientific
Stroke Center / The Neurological Institute
Columbia University
710 West 168th Street
New York
10032
United States of America
| Phone | +1 (0)212 305 8033 |
|---|---|
| jpm10@columbia.edu |
Study information
| Study design | Randomised open parallel-group international multicenter trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A Randomised trial of Unruptured Brain Arteriovenous malformations |
| Study acronym | ARUBA |
| Study objectives | 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(s) | Columbia University Medical Center Institutional Review Board, 02/11/2005, IRB# AAAB6286 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/08/2006 |
| Completion date | 01/03/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 800 |
| Total final enrolment | 226 |
| Key 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 |
| Key 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) |
| Date of first enrolment | 01/08/2006 |
| Date of final enrolment | 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
Study participating centre
10032
United States of America
Sponsor information
Government
c/o Claudia S. Moy
Neuroscience Center, Room 2214
6001 Executive Blvd., MSC9520
Bethesda MD
20892-9520
United States of America
| Website | http://www.nih.gov/ |
|---|---|
"ROR" |
https://ror.org/01s5ya894 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Institutos Nacionales de la Salud, US National Institutes of Health, NIH
- Location
- United States of America
Government organisation / National government
- Alternative name(s)
- National Institute of Neurological Disorders & Stroke, NIH/National Institute of Neurological Disorders and Stroke, NIH National Institute of Neurological Disorders and Stroke, Instituto Nacional de Trastornos Neurológicos y Accidentes Cerebrovasculares, The National Institute of Neurological Disorders and Stroke, National Institute of Neurological Disorders and Blindness, National Institute of Neurological and Communicative Disorders and Stroke, NINDS, NINDB, NINCDS
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/01/2010 | Yes | No | |
| Results article | results | 15/02/2014 | Yes | No | |
| Results article | 5-year follow-up results | 01/07/2020 | 22/06/2020 | Yes | No |
Editorial Notes
22/06/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
13/04/2016: Plain English summary added.
