Condition category
Circulatory System
Date applied
25/06/2006
Date assigned
11/09/2006
Last edited
13/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.arubastudy.org

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 measures

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

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

http://www.nih.gov/

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

Results - basic reporting

Publication summary

2010 protocol in http://www.ncbi.nlm.nih.gov/pubmed/19953376
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/24268105

Publication citations

  1. 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.

  2. 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.

Additional files

Editorial Notes

13/04/2016: Plain English summary added.