A Randomized Trial of Unruptured Brain AVMs - Full Text View

Sponsors and Collaborators:	Columbia University National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00389181

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
Unruptured Brain Arteriovenous Malformation	Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination]	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Trial of Unruptured Brain Arteriovenous Malformations

Resource links provided by NLM:

MedlinePlus related topics: Arteriovenous Malformations Radiation Therapy

U.S. FDA Resources

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

Composite event of death from any cause or symptomatic stroke (hemorrhage or infarction confirmed by imaging) [ Time Frame: from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Risk of death or clinical impairment (Rankin Score >/= 2) at 5 years post-randomization [ Time Frame: from enrollment to study end for primary outcomes of death or symptomatic stroke including hemorrhage ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	800
Study Start Date:	October 2006
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: No Intervention symptomatic medical management alone
2: Active Comparator symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy)	Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination] All interventional procedures are standard of care for the treatment of AVMs. They are not experimental. Endovascular procedures involve specially designed catheters/tubes position in the small arteries feeding blood to the AVM. The tubes are inserted into an artery in the groin and threaded up through the artery into the brain. Once positioned, the physician injects a special material that changes from liquid to solid very quickly. Once it solidifies, it blocks the artery that is feeding blood to the AVM. Neurosurgery involves the opening of a portion of the skull and the brain's outer lining to get access to the AVM. Radiosurgery involves high energy radiation (like X-rays) carefully targeted at the brain AVM to shrink it and, in the best results, eventually eliminate the artery-to-vein links and the risk of bleeding. The effect often takes one to two years to occur.

Arms

Assigned Interventions

1: No Intervention

symptomatic medical management alone

2: Active Comparator

symptomatic medical management with invasive therapies (any combination of surgery, endovascular embolization, or radiotherapy)

Procedure: invasive therapy [endovascular procedures, neurosurgery, or radiotherapy, alone or in combination]

All interventional procedures are standard of care for the treatment of AVMs. They are not experimental.

Endovascular procedures involve specially designed catheters/tubes position in the small arteries feeding blood to the AVM. The tubes are inserted into an artery in the groin and threaded up through the artery into the brain. Once positioned, the physician injects a special material that changes from liquid to solid very quickly. Once it solidifies, it blocks the artery that is feeding blood to the AVM.

Neurosurgery involves the opening of a portion of the skull and the brain's outer lining to get access to the AVM.

Radiosurgery involves high energy radiation (like X-rays) carefully targeted at the brain AVM to shrink it and, in the best results, eventually eliminate the artery-to-vein links and the risk of bleeding. The effect often takes one to two years to occur.

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:

Patient must have unruptured BAVM diagnosed by MRI/MRA and/or angiogram
Patient must be 18 years of age or older

Exclusion Criteria:

Patient has evidence of recent or prior BAVM hemorrhage
Patient has received prior BAVM therapy (endovascular, surgical, radiotherapy)
Patient has BAVM deemed untreatable by local investigator, or has concomitant vascular or brain disease that interferes with/or contradicts any invasive 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/nl) or coagulopathy (spontaneous or iatrogenic INR>1.5)
Patient is pregnant or lactating
Patient has known allergy against iodine contrast agents, multiple-foci BAVMs, or any form of arteriovenous or spinal fistulas
Patient has a diagnosed Vein of Galen type malformation, cavernous malformation, dural arteriovenous fistula, venous malformation, or 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, or hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber)

Contacts and Locations

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

Contacts

Contact: J. P. Mohr, MS, MD	212 305 8033	jpm10@columbia.edu
Contact: Alan J. Moskowitz, MD	212.569.9567	Alan.Moskowitz@MSSM.EDU

Show 57 Study Locations

Sponsors and Collaborators

Columbia University

National Institute of Neurological Disorders and Stroke (NINDS)

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
Investigator:	Deborah Ascheim, MD	InCHOIR, Department of Health Policy, Mount Sinai School of Medicine, Co-PI
Investigator:	Annetine Gelijns, PhD	InCHOIR, Department of Health Policy, Mount Sinai School of Medicine, Co-PI
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
Investigator:	Eric Vicaut, MD	Clinical Coordinating Center, Europe, Co-PI
Investigator:	Claudia S. Moy, PhD	NINDS, Co-PI

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Stapf C, Mohr JP, Choi JH, Hartmann A, Mast H. Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol. 2006 Feb;19(1):63-8. Review.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Stapf C, Mohr JP. Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke. 2007 Dec;38(12):3308-9. Epub 2007 Oct 25. No abstract available.

Responsible Party:	Columbia University Medical Center ( JP Mohr MS MD Daniel Sciarra Professor of Neurology Neurological Insitute )
Study ID Numbers:	U01NS051483, U01NS051566
Study First Received:	October 16, 2006
Last Updated:	April 3, 2009
ClinicalTrials.gov Identifier:	NCT00389181 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

unruptured brain arteriovenous malformation
AVM
BAVM
Stroke
Intracranial Hemorrhage

Study placed in the following topic categories:

Cardiovascular Abnormalities
Aneurysm
Cerebral Infarction
Vascular Malformations
Stroke
Vascular Diseases

Hemangioma
Arteriovenous Malformations
Intracranial Hemorrhages
Hemorrhage
Congenital Abnormalities

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Cardiovascular Abnormalities
Aneurysm
Vascular Malformations
Neoplasms, Vascular Tissue

Vascular Diseases
Hemangioma
Cardiovascular Diseases
Arteriovenous Malformations
Congenital Abnormalities

ClinicalTrials.gov processed this record on July 02, 2009