Primary: To determine whether medical management improves long-term outcomes of patients with unruptured BAVMs compared to invasive therapy (with endovascular procedures, neurosurgery, or radiotherapy, alone or in ombination). The trial has been…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Vascular therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Composite event of death from any cause or stroke (hemorrhage or infarction
revealed by imaging). Clinical outcome status will be measured by the Rankin
Scale, a widely-used outcome measure for stroke.
Secondary outcome
The secondary measures of outcome include adverse events, quality of life and
cost.
Background summary
Current invasive therapy for brain arteriovenous malformations (BAVMs) is
varied and includes endovascular procedures, neurosurgery, and radiotherapy
alone and in combination, largely dependent on the decisions of the local
clinical team. All of these invasive therapies are administered on the
assumption that they will decrease the risk of initial or subsequent hemorrhage
and lead to better long-term outcomes. Despite these laudable goals, the
literature contains almost no reference to the outcome for medical management
before or after hemorrhage, or for intervention outcome for unruptured BAVMs.
The most contentious issue at present is whether invasive therapy should be
considered for those increasingly being discovered incidentally by brain
imaging, with lesions that have not bled.
Study objective
Primary: To determine whether medical management improves long-term outcomes of
patients with unruptured BAVMs compared to invasive therapy (with endovascular
procedures, neurosurgery, or radiotherapy, alone or in ombination). The trial
has been designed to test whether medical management or invasive therapy will
reduce the risk of death or stroke (due to hemorrhage or infarction) by at
least 40% (an absolute magnitude of about 7.5% over 5 years). It will require
800 patients to detect the hypothesized 40% reduction in event rate, analyzed
using the intention-to-treat principal. This sample size will support a test
of non-inferiority if the medical management is not superior to invasive
therapy.
Secondary: To compare the impact of medical management to invasive therapy with
respect to adverse events, quality of life and cost
Study design
The study design is a prospective, multi-center, parallel design, randomized,
controlled trial. Treatment assignment will not be masked; however, clinical
coordinating center personnel and outcome events committees will be blinded to
treatment assignment.
Intervention
The invasive therapy arm of the trial involves prophylactic efforts with a plan
for
eradication of the observed BAVM utilizing endovascular procedures,
microsurgery, or radiosurgery, alone or in combination with pharmacological
therapy for existing risk factors and coexisting medical conditions. The
medical management arm will involve pharmacological therapy as deemed
appropriate for medical symptoms.
Study burden and risks
Participants are expected to visit the outpatient clinic for follow-up visits
every 6 months in the first two years and on a yearly basis thereafter for a
maximum period of 7.5 years. After the first two years, ther will be a yearly
follow-up by telephone as well.
Medical management or interventional treatment with medical management are both
well recognized clinical options. Both are accepted ways to treat AVMs. Neither
approach is considered experimental. It is not known whether medical management
alone or interventional treatment with medical management is better.
The principal risk from an AVM is the occurrence of a stroke. This can occur if
the AVM ruptures and significant bleeding occurs. This risk is present whether
one is treated medically or has an interventional procedure(s). The risk of
stroke is between 1% and 8% per year for individuals with an AVM who have
medical management. For patients with an AVM who have one or more
interventional procedures, the risk of stroke may be between 4 and 9% per year
in the first years.
The interventions themselves carry a small risk as well. The principal risk to
all of the procedures is the risk of hemorrhage in the brain that may result in
new neurological deficits, or death.
For endovascular treatment, bleeding may occur in the groin, the standard site
for all angiograms. Emboli may occlude cerebral vessels and lead to brain
infarction.
Neurosurgery for brain AVMs carries a small risk that healthy brain tissues may
be displaced and damaged during the approach to the site of the brain AVM.
Radiotherapy for brain AVMs carries the same risks as radiotherapy to the head
and brain for treatment of other conditions, such as brain tumors. For AVM, the
doses are usually lower than those used for brain tumors but it is possible the
radiation can cause injury to the arteries and veins around the AVM that
results in bleeding to occur before the effects of the radiation reduce the
blood supply to the malformation. In addition, hair loss in the path of the
beam can occur. Finally, the radiation may cause damage to healthy brain tissue
adjacent to the AVM.
710 West 168th Street
New York, NY 10032
US
710 West 168th Street
New York, NY 10032
US
Listed location countries
Age
Inclusion criteria
1. Patient must have an unruptured BAVM diagnosed by MRI/MRA and/or angiogram
2. Patient must be 18 years of age or older
3. Patient must have signed Informed Consent Form
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 *2
5. Patient has concomitant disease reducing life expectancy to less than 10 years
6. Patient has thrombocytopenia (< 100,000/nl),
7. Patient has coagulopathy (spontaneous or iatrogenic INR>1.5, PT>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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ISRCTN | ISRCTN44013133 |
| CCMO | NL14909.041.06 |