A Randomized Trial of Unruptured Brain AVMs (ARUBA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jay Preston Mohr, Columbia University
ClinicalTrials.gov Identifier:
NCT00389181
First received: October 16, 2006
Last updated: June 2, 2015
Last verified: June 2015
  Purpose

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 Intervention Phase
Arteriovenous Malformations, Cerebral
Procedure: Interventional therapy
Other: Medical management
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Difference of 5-year event rates between two arms [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    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)


Enrollment: 226
Study Start Date: October 2006
Study Completion Date: May 2015
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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 contraindicates any interventional therapy type (stenosis/occlusion of neck artery, prior brain surgery/radiation for other reasons)
  4. Patient has baseline Rankin ≥2
  5. Patient has concomitant disease reducing life expectancy to less than 10 years
  6. Patient has thrombocytopenia (< 100,000/μL),
  7. Patient has uncorrectable coagulopathy (INR>1.5)
  8. Patient is pregnant or lactating
  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

    Previous diagnosis of any of the following -

  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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389181

  Show 66 Study Locations
Sponsors and Collaborators
Columbia University
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
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jay Preston Mohr, Daniel Sciarra Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT00389181     History of Changes
Other Study ID Numbers: AAAB6286, U01NS051566, U01NS051483
Study First Received: October 16, 2006
Last Updated: June 2, 2015
Health Authority: United States: Federal Government

Keywords provided by Columbia University:
Unruptured brain arteriovenous malformation
AVM
BAVM
Stroke
Intracranial Hemorrhage

Additional relevant MeSH terms:
Arteriovenous Malformations
Congenital Abnormalities
Intracranial Arteriovenous Malformations
Cardiovascular Abnormalities
Central Nervous System Vascular Malformations
Nervous System Malformations
Vascular Malformations
Hemangioma
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Arterial Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Vascular Tissue
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on June 29, 2015