Novel embolization agent “promising” for the endovascular treatment of cerebral aneurysms in animal model

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embolization
Ruben Mühl-Benninghaus

The first preclinical study of a novel embolization agent, GPX, reports its successful performance in a rabbit aneurysm model. High rates of complete angiographic occlusion were achieved and maintained, said Ruben Mühl-Benninghaus (Saarland University Hospital, Homburg, Germany), presenting these “promising” results at the 2019 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (7–11 September, Barcelona, Spain).

In recent years, liquid embolic agents have emerged for endovascular treatment of cerebral aneurysm. “There are multiple liquid embolics available right now”, Mühl-Benninghaus said, before describing the properties of the ideal embolic agent: “It should have good control and precision during embolic injection, it should not adhere to any adhesion or clumping within the catheter, and the penetration of the liquid embolic agent should always target the distal vessel, which is the aim of the occlusion. Ease of use is also very important, [to] minimise the preparation steps and minimise complications during preparation. Of course, no fragmentation and no reflux should be achieved in the optimal liquid agent.”

Introducing the CIRSE audience to GPX, he described it as a polymer in a hypersaline solution, which solidifies upon injection into the blood vessel in response to a decreased sodium chloride concentration. The agent is prepackaged in a single, standard syringe and comes with an empty syringe. The interventionalist connects the two syringes and needs to mix them 25 times before the agent is ready to use. “Due to its waterborne composition, no specialised catheters are needed and no DMSO [dimethyl sulfoxide] and no vortexing prior to the procedure is required”, Mühl-Benninghaus explained.

In the present, pre-clinical study, the investigators set out to assess the in vivo performance of the GPX in a rabbit model.

To this end, elastase-induced aneurysms were created in 10 New Zealand white rabbits. Each aneurysm was embolized with low viscosity GPX using an Echelon 10 microcatheter (Medtronic) with balloon assistance. The mean aneurysm neck diameter, width, and height were 3.6±1mm, 3±0.8mm, and 7.4±1.4mm, respectively. The mean dome-to-neck ratio was 0.9±0.2.

Ninety per cent of aneurysms (nine of 10) showed complete stagnation of intra-aneurysmal flow within 30 minutes of device deployment. One aneurysm showed moderately diminished intra-aneurysmal flow within 30 minutes due to distal migration of GPX that still was connected to intra-aneurysmal embolic. This was assessed via digital subtraction angiography (DSA), performed predeployment, as well as five, 10, and 30 minutes post-deployment.

DSA was also performed one month after the procedure in the eight surviving rabbits (two of the study animals did not survive to one-month post-procedure). All eight aneurysms were completely occluded.

“We did not see microscopically any fragmentation of GPX, and we did not see any adhesion to the catheter or the balloon”, Mühl-Benninghaus noted. “We did observe some resistance during injection from the new embolic agent through the Echelon 10 microcatheter. Our impression was that there was a little varying visibility of GPX.”

“Upon gross examination at 28-days, tissue appeared normal”, he reported. Histological examination of the vessel wall, however, did reveal “evidence of some inflammation reaction”, but Mühl-Benninghaus said that he did “not have the final results”.

Compared to stent-assisted coil embolization in the same model, Mühl-Benninghaus said that the occlusion rates achieved with GPX were similar. “We have also performed previously in the same model the same thing with onyx, and we did see less fragmentation with GPX. We did not use any remodelling balloon due to the cost of balloons. The remodelling balloons could provide better stability of the microcatheter. For further investigations, this might be an option.”

When concluding, he outlined some limitations of the present study. Namely, the small study population, and the outstanding final histological results. He summarised that while GPX was easy to use and did not require DMSO, the agent’s viscosity needs improving, and although it has the potential to achieve durable occlusion of cerebral aneurysms, its clinical relevance will have to be assessed in larger and longer-term studies.

“It looks to us to be a promising embolic agent for neuro-intervention therapy,” he stated. embolization embolization


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