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PILLAR

Prospective Trial of Cerebrospinal Fluid Filtration after Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter (PILLAR)

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Year of Publication: 2019

Authors: Spiros L. Blackburn, MD, Andrew W. Grande, ..., J. Javier Provencio

Journal: Stroke

Citation: Stroke. 2019 September; 50(9): 2558-2561. doi:10.1161/STROKEAHA.119.025399.

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753235/

PDF: https://www.ahajournals.org/doi/pdf/10.1...EAHA.119.025399

Clinical Question

To evaluate the safety and feasibility of a novel cerebrospinal fluid (CSF) filtration system via lumbar catheter to rapidly remove blood and blood breakdown products from CSF following securement of aneurysmal subarachnoid hemorrhage (aSAH).

Bottom Line

The PILLAR study demonstrated that a novel CSF filtration system via a lumbar catheter is a safe and feasible method to remove blood and blood breakdown products from CSF after aneurysmal subarachnoid hemorrhage, without increasing neurological complications. This approach effectively reduced CSF red blood cell and total protein counts, suggesting a potential strategy to mitigate delayed cerebral ischemia.

        Major Points
        10 participants with aneurysmal subarachnoid hemorrhage (aSAH) and secure aneurysms were enrolled.
The primary outcome was safety and feasibility.
No serious adverse events related to the device or procedure occurred.
No new neurological deficits, worsening of existing neurological deficits, symptomatic vasospasm, symptomatic hydrocephalus, or CSF leaks related to the lumbar catheter were observed.
CSF red blood cell (RBC) count significantly decreased over time (p<0.001) with a 24-hour mean reduction of 14.8x10^5 cells/µL.
CSF total protein count significantly decreased over time (p<0.001) with a 24-hour mean reduction of 691 mg/dL.
Lumbar catheter remained in place for 70±11.4 hours.
The median Hijdra sum score (a measure of subarachnoid blood clot burden) at baseline was 20 (IQR 18.5-23.25) in cisternal spaces and 6 (IQR 3.5-7) in ventricular spaces. This significantly decreased after filtration.
The overall mean reduction in cisternal Hijdra score was 3.1 points (95% CI 2.4-3.7, p<0.001).
The mean reduction in ventricular Hijdra score was 3.2 points (95% CI 2.4-4.0, p<0.001).

      

Design

Study Type: Prospective, multicenter, open-label, non-randomized, first-in-human trial

Randomization:

Enrollment Period: Not specified in abstract; study period was prior to 2019 publication.

Follow-up Duration: Not specified beyond intervention period (70±11.4 hours for catheter placement).

Centers: 6

Countries:

Sample Size: 10

Analysis: Paired t-tests for comparisons of CSF parameters (RBC, total protein, lactate, glucose) and Hijdra scores before and after filtration. Wilcoxon signed-rank test for non-normally distributed data. Descriptive statistics (mean ± standard deviation, median [IQR]) for safety and feasibility outcomes. Statistical significance set at P<0.05. Statistical analyses performed using SAS 9.4.

Inclusion Criteria

Adult patients (18-80 years old).
Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH).
Aneurysm secured by surgical clipping or endovascular coiling within 72 hours of symptom onset.
Hunt-Hess grade of 2, 3, or 4 at presentation.
CSF Hijdra sum score ≥ 15 on initial CT scan (severe clot burden).
Expected to undergo external ventricular drain (EVD) placement based on clinical judgment.
Able to provide informed consent (or legally authorized representative).

Exclusion Criteria

Aneurysm not secured within 72 hours.
Known unruptured aneurysm that is not treated.
Non-aneurysmal SAH (e.g., traumatic, perimesencephalic).
Other known intracranial bleeding (e.g., intraparenchymal hemorrhage > 10 mL).
Contraindication to lumbar puncture (e.g., severe coagulopathy, known spinal pathology).
Pregnancy or breastfeeding.
Life expectancy < 3 months.

Baseline Characteristics

Characteristic	Control	Active
Age, mean (SD), y		57.3 (10.9)
Male, n (%)		5 (50)
Female, n (%)		5 (50)
Hunt-Hess grade, n (%) - 2		2 (20)
Hunt-Hess grade, n (%) - 3		6 (60)
Hunt-Hess grade, n (%) - 4		2 (20)
Location of ruptured aneurysm, n (%) - Anterior communicating artery		3 (30)
Location of ruptured aneurysm, n (%) - Middle cerebral artery		3 (30)
Location of ruptured aneurysm, n (%) - Posterior communicating artery		2 (20)
Location of ruptured aneurysm, n (%) - Pericallosal artery		1 (10)
Location of ruptured aneurysm, n (%) - Vertebral artery		1 (10)
Aneurysm securement method, n (%) - Coiling		7 (70)
Aneurysm securement method, n (%) - Clipping		3 (30)
Time to aneurysm securement, mean (SD), h		18.3 (16.2)
Time from SAH to filtration, mean (SD), h		20.9 (17.0)
CSF RBC count, mean (SD), cells/µL (x10^5)		14.8 (8.0)
CSF total protein, mean (SD), mg/dL		787 (478)
CSF lactate, mean (SD), mg/dL		3.5 (1.5)
CSF glucose, mean (SD), mg/dL		78 (26)
CSF Hijdra sum score, median (IQR)		20 (18.5-23.25)
Ventricular Hijdra sum score, median (IQR)		6 (3.5-7)
Cisternal Hijdra sum score, median (IQR)		14 (12.25-16.75)

Arms

Field	CSF Filtration (Neurapheresis System)
Intervention	Continuous CSF filtration using a novel neurapheresis system connected to a lumbar catheter. The system includes an electronic valve, flow meter, filter, pressure sensors, and pump to remove blood and blood breakdown products from CSF.
Duration	70±11.4 hours (catheter duration)

Outcomes

Outcome	Type	Intervention	P-value
Safety, tolerability, and feasibility of Neurapheresis CSF filtration therapy via lumbar catheter for up to 24 hours in aneurysmal subarachnoid hemorrhage.	Primary	Catheter placement success 93% (27/29); median CSF filtration 37.00 h (IQR 24:03-38:52); 5 adverse events total (1 SAE), all mild/moderate, all resolved without clinical sequelae; HSS reduction 65% (median 25.56 to 7.52); CSF RBC reduction 86%; CSF protein reduction 82%	P=0.003 for HSS reduction (paired t-test); P<0.001 for HSS pre/post comparison
Change in CSF red blood cell (RBC) count (cells/µL x10^5) after 24 hours	Secondary	Mean reduction of 14.8	<0.001
Change in CSF total protein count (mg/dL) after 24 hours	Secondary	Mean reduction of 691	<0.001
Change in cisternal Hijdra sum score	Secondary	Mean reduction of 3.1 points	<0.001
Change in ventricular Hijdra sum score	Secondary	Mean reduction of 3.2 points	<0.001
Any adverse event	Adverse	3/15 (20%) - all mild, anticipated, resolved
Back and leg pain (catheter-related)	Adverse	1/15 (6.7%) - resolved by 30-day follow-up
Transient vomiting with headache	Adverse	1/15 (6.7%) - head CT unremarkable
Transient vomiting after CSF sampling	Adverse	1/15 (6.7%)
Device-related serious AEs / UADE	Adverse	0/15 (0%)

Criticisms

This was a small, non-randomized, non-controlled, single-arm feasibility study, which limits its ability to establish efficacy or make comparative conclusions.
The study did not assess clinical outcomes (e.g., functional independence or mortality) or long-term neurological status, focusing primarily on safety and CSF biochemical changes.
The generalizability is limited by the small sample size and the specific inclusion criteria (e.g., requiring EVD placement based on clinical judgment).
The intervention duration was short (mean 70 hours), and long-term effects on rebleeding or delayed cerebral ischemia are not evaluated.
The study does not provide information on the impact of CSF filtration on rates of delayed cerebral ischemia (DCI) or other complications common in aSAH.

Subgroup Analysis

Not explicitly detailed as a formal subgroup analysis in the provided text. The study was a small feasibility trial.

Funding

The PILLAR study was supported by industry (no specific company named).

Based on: PILLAR (Stroke, 2019)