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BRAT

The Barrow Ruptured Aneurysm Trial

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Year of Publication: 2011

Authors: Cameron G. McDougall, Robert F. Spetzler, Joseph M. Zabramski, ..., Felipe C. Albuquerque

Journal: Journal of Neurosurgery

Citation: J Neurosurg. November 4, 2011

PDF: https://www.researchgate.net/profile/Rob...saWNhdGlvbiJ9fQ

Clinical Question

Is one treatment modality (surgical clipping or endovascular coil embolization) superior to the other for treatment of acutely ruptured cerebral aneurysms, as measured by clinical and angiographic outcomes?

Bottom Line

At 1 year after treatment, a policy of intent to treat favoring coil embolization resulted in significantly fewer poor outcomes (10.5% absolute difference) compared to surgical clipping (23.2% vs 33.7%, OR 1.68, p = 0.02). Although most aneurysms assigned to the coil group were treated by coil embolization (62.3%), a substantial number crossed over to surgical clipping. No patient treated by coil embolization suffered recurrent hemorrhage during the first year. High-quality surgical clipping remains important as an alternative treatment modality.

        Major Points
        Single-center prospective randomized controlled trial comparing surgical clipping vs endovascular coil embolization for ruptured intracranial aneurysms
725 patients screened, 500 enrolled with informed consent, 471 eligible for analysis (238 assigned to clip, 233 assigned to coil)
No anatomical exclusions - all patients with aneurysmal SAH were eligible regardless of aneurysm location or characteristics
Intent-to-treat design with crossover allowed based on treating surgeon's clinical judgment
Primary outcome: poor outcome defined as mRS score > 2 (death or dependency) at 1 year
At 1 year, 33.7% of patients assigned to clipping had poor outcomes vs 23.2% assigned to coiling (OR 1.68, 95% CI 1.08-2.61, p = 0.02)
When only patients receiving assigned treatment analyzed: 33.9% clip vs 18.4% coil had poor outcomes (OR 2.28, p = 0.005)
75 patients crossed over from coil to clip (most common reasons: anatomical features unfavorable for coiling, hematoma requiring evacuation, or multiple aneurysms with uncertain rupture source)
Patients who crossed over from coil to clip had same outcomes as those assigned to and treated with clipping
No rebleeding occurred in any patient treated by coil embolization during first year
Retreatment more common in coil group: 10.62% vs 4.49% in clip group at 1 year (OR 2.57, p = 0.03)
Age > 50 years and Hunt & Hess grade > II were independent predictors of poor outcome
Results consistent with ISAT findings despite different trial design and broader inclusion criteria

      

Design

Study Type: Prospective randomized controlled trial

Randomization: 1

Blinding: Outcome assessments performed by independent nurse practitioners not involved in treatment, but assessors were not blinded to treatment modality

Enrollment Period: March 2003 to January 2007

Follow-up Duration: 1 year (with planned follow-up to 6 years)

Centers: 1

Countries: United States

Sample Size: 471

Analysis: Intent-to-treat analysis using logistic regression methods. Multivariable models adjusted for age > 50 years and Hunt & Hess score > II. Secondary analyses examined outcomes based on actual treatment received. Wilcoxon rank-sum test for continuous variables and Mantel-Haenszel chi-square test for categorical variables.

Inclusion Criteria

Age 18-80 years
Admitted to ICU with acute nontraumatic subarachnoid hemorrhage
SAH confirmed by CT scan or lumbar puncture
Presentation within 14 days of hemorrhage
Patient or health care decision surrogate provided informed consent
No anatomical exclusions - all aneurysm locations and sizes included

Exclusion Criteria

Traumatic subarachnoid hemorrhage
Presentation more than 14 days after hemorrhage
Age < 18 years or > 80 years

Baseline Characteristics

Characteristic	Control	Active
Total patients	238	233
Mean age (years)	53.1 ± 12.8	54.3 ± 12.0
Female	69.7%	71.2%
Race - Caucasian	63.9%	67.8%
Race - Hispanic	26.5%	21.5%
Race - African American	5.5%	3.9%
Race - Asian	1.3%	3.4%
Race - Other	2.9%	3.4%
Diabetes	8.4%	7.3%
Hypertension	43.3%	44.6%
Smoking history	61.8%	62.2%
Cocaine use	8.8%	9.0%
Methamphetamine use	7.1%	8.6%
Mean GCS score	12.3 ± 3.6	12.5 ± 3.6
Mean Hunt & Hess grade	2.6 ± 1.1	2.6 ± 1.1
Mean Fisher grade	2.7 ± 0.7	2.7 ± 0.6
Aneurysm mean size (mm)	6.8 ± 4.1	6.6 ± 4.0
Aneurysm median size (mm)	6.0 (IQR 4-8)	6.0 (IQR 4-8)
Posterior circulation aneurysm	16.0%	13.7%
Anterior circulation aneurysm	73.1%	72.5%
Angiography negative	10.9%	13.3%
Hunt & Hess Grade I	13.4%	13.3%
Hunt & Hess Grade II	38.7%	39.9%
Hunt & Hess Grade III	29.8%	26.2%
Hunt & Hess Grade IV	12.2%	14.6%
Hunt & Hess Grade V	5.9%	6.0%

Arms

Field	Control	Endovascular Coil Embolization
Intervention	Microsurgical clipping of ruptured intracranial aneurysm. Patients assigned to surgical clipping service in alternating fashion. Crossover to endovascular coiling allowed if treating surgeon determined it would provide better outcome. When possible, aneurysm treated within 24 hours of admission. All patients received standardized pre- and postoperative care including external ventricular drainage as needed and vasospasm prophylaxis and treatment.	Endovascular coil embolization of ruptured intracranial aneurysm. Patients assigned to endovascular service in alternating fashion. Crossover to surgical clipping allowed if treating surgeon determined aneurysm more appropriate for surgical treatment (e.g., anatomical features unfavorable for coiling, need for hematoma evacuation, multiple aneurysms with uncertain rupture source). When possible, aneurysm treated within 24 hours of admission. First-generation Matrix coils used in majority of procedures. All patients received standardized pre- and postoperative care including external ventricular drainage as needed and vasospasm prophylaxis and treatment.
Duration	Treatment during acute hospitalization, with 1-year follow-up	Treatment during acute hospitalization, with 1-year follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Poor outcome defined as modified Rankin Scale (mRS) score > 2 at 1 year, indicating death or dependency	Primary	69 of 205 patients (33.7%)	46 of 198 patients (23.2%)	10.50%	0.02
Poor outcome (mRS > 2) at 1 year - patients who received assigned treatment only	Secondary	61 of 180 patients (33.9%)	20 of 109 patients (18.4%)	OR 2.28	0.005
Poor outcome (mRS > 2) at 1 year - actual treatment received (all treated patients)	Secondary	83 of 245 patients treated with clip (33.9%)	23 of 113 patients treated with coil (20.4%)	OR 2.01	0.01
Rebleeding before treatment	Secondary	2 patients	0 patients
Rebleeding after treatment during initial hospitalization	Secondary	1 patient assigned to clip	1 patient assigned to coil but crossed over to clip
Rebleeding during first year after treatment	Secondary	No rebleeding in clip-treated patients after initial hospitalization	0 patients treated with coil
Retreatment by 1 year - intent-to-treat	Secondary	7 of 238 (2.94%)	16 of 232 (6.9%)	OR 2.44	0.05
Retreatment by 1 year - actual treatment	Secondary	11 of 245 (4.49%)	12 of 113 (10.62%)	OR 2.57	0.03
Crossover from assigned coil to clip treatment	Secondary		75 of 199 treated patients (37.7%)
Crossover from assigned clip to coil treatment	Secondary	4 patients
Poor outcome in patients who crossed from coil to clip	Secondary	22 of 65 (33.9%) - same as clip/clip group
Death before treatment	Adverse	3 patients	3 patients
Retreatment during initial hospitalization	Adverse	5 patients assigned to clip (2.10%)	7 patients assigned to coil (3.02%)	OR 1.45	0.53

Subgroup Analysis

Multivariable analysis showed that age > 50 years (OR 2.03, 95% CI 1.23-3.42, p = 0.007) and Hunt & Hess grade > II (OR 3.51, 95% CI 2.21-5.68, p < 0.0001) were each independently associated with poor outcome at 1 year, regardless of treatment modality. No significant interactions between treatment modality and either age or baseline Hunt & Hess score were found. For good grade patients (Hunt & Hess I-II), poor outcomes were 9.4% for coil and 19.8% for clip groups.

Criticisms

Single-center study limits generalizability
Not powered sufficiently to demonstrate definitive differences - designed as pilot study
Outcome assessors not blinded to treatment modality
Substantial crossover (37.7%) from coil to clip group, though this was by design
Decisions about crossing over somewhat subjective and may vary across institutions
First-generation Matrix coils used in majority of coil procedures have since been withdrawn from market due to high recurrence rates
No patient lost to 1-year follow-up data collection for 68 patients (14.4%)
Relatively small sample size compared to ISAT
Higher proportion of poor grade patients (19.3% Hunt & Hess IV-V) compared to ISAT (12% WFNS IV-V)
Cannot determine if incomplete coil occlusion of complex aneurysms would increase complication or recurrence rates
Angiographic outcomes not yet reported at 1 year

Funding

Not specified in manuscript

Based on: BRAT (Journal of Neurosurgery, 2011)

Authors: Cameron G. McDougall, Robert F. Spetzler, Joseph M. Zabramski, ..., Felipe C. Albuquerque

Citation: J Neurosurg. November 4, 2011

Content summarized and formatted by NeuroTrials.ai.

BRAT

(2011)

Objective

To compare the safety and efficacy of clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes.

Study Summary

• At 1 year, coil embolization resulted in 10.5% fewer poor outcomes compared to surgical clipping (23.2% vs 33.7%, OR 1.68, p = 0.02)
• Of aneurysms assigned to coil group, 62.3% were actually treated by coil embolization, with substantial crossover to surgical clipping
• No patient treated by coil embolization suffered recurrent hemorrhage during the first year

Intervention

Patients were assigned in alternating fashion to either surgical aneurysm clipping or endovascular coil embolization, with crossover allowed based on clinical judgment

Inclusion Criteria

Patients aged 18-80 years admitted to ICU with acute nontraumatic subarachnoid hemorrhage (confirmed by CT scan or lumbar puncture) within 14 days of hemorrhage

Study Design

Arms: Surgical clipping vs Endovascular coil embolization

Patients per Arm: 238 assigned to clip, 233 assigned to coil

Outcome

• Poor outcome (mRS > 2) at 1 year: 33.7% in clip group vs 23.2% in coil group (OR 1.68, 95% CI 1.08-2.61, p = 0.02)
• When only patients who received assigned treatment analyzed: 33.9% clip vs 18.4% coil (OR 2.28, p = 0.005)
• Retreatment by 1 year: 6.9% in coil group vs 2.94% in clip group on intent-to-treat basis

Bottom Line

Major Points

Single-center prospective randomized controlled trial comparing surgical clipping vs endovascular coil embolization for ruptured intracranial aneurysms
725 patients screened, 500 enrolled with informed consent, 471 eligible for analysis (238 assigned to clip, 233 assigned to coil)
No anatomical exclusions - all patients with aneurysmal SAH were eligible regardless of aneurysm location or characteristics
Intent-to-treat design with crossover allowed based on treating surgeon's clinical judgment
Primary outcome: poor outcome defined as mRS score > 2 (death or dependency) at 1 year
At 1 year, 33.7% of patients assigned to clipping had poor outcomes vs 23.2% assigned to coiling (OR 1.68, 95% CI 1.08-2.61, p = 0.02)
When only patients receiving assigned treatment analyzed: 33.9% clip vs 18.4% coil had poor outcomes (OR 2.28, p = 0.005)
75 patients crossed over from coil to clip (most common reasons: anatomical features unfavorable for coiling, hematoma requiring evacuation, or multiple aneurysms with uncertain rupture source)
Patients who crossed over from coil to clip had same outcomes as those assigned to and treated with clipping
No rebleeding occurred in any patient treated by coil embolization during first year
Retreatment more common in coil group: 10.62% vs 4.49% in clip group at 1 year (OR 2.57, p = 0.03)
Age > 50 years and Hunt & Hess grade > II were independent predictors of poor outcome
Results consistent with ISAT findings despite different trial design and broader inclusion criteria

Study Design

Study Type: Prospective randomized controlled trial
Randomization: Yes
Blinding: Outcome assessments performed by independent nurse practitioners not involved in treatment, but assessors were not blinded to treatment modality
Sample Size: 471
Follow-up: 1 year (with planned follow-up to 6 years)
Centers: 1
Countries: United States

Primary Outcome

Definition: Poor outcome defined as modified Rankin Scale (mRS) score > 2 at 1 year, indicating death or dependency

Control	Intervention	HR/OR	P-value
69 of 205 patients (33.7%)	46 of 198 patients (23.2%)	- (1.08-2.61)	0.02

Limitations & Criticisms

Single-center study limits generalizability
Not powered sufficiently to demonstrate definitive differences - designed as pilot study
Outcome assessors not blinded to treatment modality
Substantial crossover (37.7%) from coil to clip group, though this was by design
Decisions about crossing over somewhat subjective and may vary across institutions
First-generation Matrix coils used in majority of coil procedures have since been withdrawn from market due to high recurrence rates
No patient lost to 1-year follow-up data collection for 68 patients (14.4%)
Relatively small sample size compared to ISAT
Higher proportion of poor grade patients (19.3% Hunt & Hess IV-V) compared to ISAT (12% WFNS IV-V)
Cannot determine if incomplete coil occlusion of complex aneurysms would increase complication or recurrence rates
Angiographic outcomes not yet reported at 1 year

Citation

J Neurosurg. November 4, 2011

View Original Publication →

BRAT

The Barrow Ruptured Aneurysm Trial

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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