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Ahead of the COATING study’s much-anticipated final analyses, principal investigator Laurent Pierot (Reims University Hospitals, Reims, France) sits down with NeuroNews to outline the “tremendous impact” he feels its results will have on the interventional treatment of intracranial aneurysms.
The use of single antiplatelet therapy (SAPT) alongside a flow diverter in intracranial aneurysm treatment is by no means a totally novel concept. Relying on knowledge and experience alone, some operators already adopt this approach in their practice—but do so in an ‘off-label’ fashion, as flow-diverter treatments are currently only indicated when paired with dual antiplatelet therapy (DAPT).
According to Pierot, however, this could all be about to change. As a prospective, multicentre randomised controlled trial (RCT) directly comparing aneurysm treatments with a surface-modified or ‘coated’ flow diverter plus SAPT versus a ‘bare’ flow diverter plus DAPT, COATING represents a first-of-its-kind study, and is set to provide concrete evidence on the safety of the former of these two approaches.
“Some people—as with stenting—are using SAPT in certain flow-diverter cases,” Pierot says. “But, if you have a complication, you will be in a position that will be a little bit difficult, because it’s not what is written in the IFU [instructions for use].”
He goes on to note that the use of SAPT rather than DAPT alongside coated flow diverters like WallabyPhenox’s p64 MW Hydrophilic Polymer Coating (HPC) device is currently authorised in very specific aneurysm cases, such as those where there appear to be no other viable interventional options. However, a positive finding regarding the company’s HPC surface modification technology in COATING would likely expand today’s indications far beyond this ‘last-resort’ paradigm, enabling surface-modified flow diverters to be deployed with SAPT across a wide array of both ruptured and unruptured aneurysms.
“It’s probably something we will have to do at some point [in the future], if the study is positive—to collect cases of ruptured and unruptured aneurysms with p64 MW HPC, or p48 MW HPC, just to confirm that it is feasible and we have a rate of rebleeding that is in line with other techniques,” Pierot adds.
COATING nears completion
The COATING RCT involves patients with unruptured or recanalised intracranial aneurysms indicated for endovascular treatment via placement of a flow diverter. Across 25 European centres, patients meeting the study’s inclusion criteria are being enrolled and randomised 1:1 to undergo intervention with either the p64 MW HPC—WallabyPhenox’s surface-modified flow diverter—or the regular, ‘uncoated’ p64 MW device. The former group is receiving SAPT alongside flow-diversion treatment, while the latter is receiving DAPT.
Having begun enrolment in 2021, COATING is now just a handful of patients away from reaching its final target of 170—a goal that was settled on following an interim assessment at the 85-patient mark and safety analyses at the 140-patient milestone. Neither of these evaluations revealed any major safety issues and a data safety monitoring board (DSMB) therefore greenlit continuation of the study.
Pierot reports that a total of 156 patients have already been enrolled, stating that he hopes enrolment will be complete by September of this year, with initial primary-endpoint and safety data anticipated towards the end of 2024 or at the start of 2025.
Key endpoints
Relative to many other large-scale RCTs, COATING has been able to enrol, treat and evaluate its patient population “very rapidly”. Pierot attributes the speedy analysis of these patients to the short timeframe forming part of the study’s primary endpoint: the number of diffusion-weighted imaging (DWI) lesions visualised on magnetic resonance imaging within 48 hours of the index procedure.
“Usually, I am not very much in favour of having a primary endpoint that is not clinical,” he concedes. “The goal of surface modification is to reduce thromboembolic complications, but the rate of these complications is not so high—between 5–10%. So, if you want to see a difference between two groups, you need to have a very high number of patients, which is not feasible.”
Here, Pierot touches on an even more vital advantage carried by DWI lesions as an endpoint, stating that these ‘spots’ on imaging—an adjunct for the safety of an endovascular aneurysm treatment—occur far more frequently compared to clinical outcomes like actual procedural complications or patient symptoms. DWI lesions are present in roughly 50% of cases, and COATING’s investigators believe this relatively high prevalence will enable the study to be conducted across a more limited number of patients while still revealing meaningful between-group differences.
Pierot goes on to say that COATING represents the first time a study dedicated to intracranial aneurysm treatment has been based around DWI lesions, adding that it is a “very original” endpoint and constitutes a “really new way” to conduct these assessments. As such, COATING will not only provide insights on HPC, and surface modification more generally, but it will also show researchers “how to optimise DWI to evaluate these kinds of populations”.
“The main goal of COATING is safety,” Pierot continues. “We have efficacy already—we are just covering the flow diverter and not changing the mechanical properties of the device, which means the [efficacy-related] results will be the same as with a bare version of the flow diverter. The main question is safety. Can we use a surface-modified flow diverter with a single antiplatelet treatment? It’s a very important question, and this will be the first time we have an answer.”
This primary endpoint is “the most important aspect, but it will not summarise all findings of the study”, Pierot also notes, alluding to COATING’s myriad of secondary safety and efficacy endpoints, which include but are not limited to rates of mortality/ morbidity, neurological stroke or death, intracranial haemorrhage (ICH), technical success, target aneurysm retreatment or recurrence, and in-stent stenosis and/or thrombosis at the target site.
“We are not expecting [to have] a negative primary endpoint finding—but, even if we do, we will have all of the secondary endpoints to analyse and give us a lot of information regarding the use of surface-modified flow diverters,” he comments.
New frontiers
The fundamental motive behind COATING is to enable flow-diverter treatments with SAPT rather than DAPT; the former is associated with fewer bleeding complications and a reduced overall medication burden for the patient. And, as previously stated, while flow diversion with SAPT is utilised in certain cases already, positive findings within the COATING study will allow WallabyPhenox to make p64 MW HPC the most widely indicated surface-modified flow diverter, meaning a far greater array of patients can benefit from SAPT only alongside the device. This milestone may, in turn, convince more physicians of the significant role surface modification can play in aneurysm care too.
“We will no longer be obliged to use DAPT with this flow diverter, which will potentially lead to the [wider] indication of the device,” Pierot explains. “We have to accept one thing: as of now, the most efficacious treatment for intracranial aneurysms is flow diversion. It is the best treatment, at least in terms of efficacy, and you have to use the best treatment as much as you can.”
Here, Pierot reiterates his belief that COATING could be the catalyst for flow diversion to become a more accepted and widely used treatment for ruptured and unruptured aneurysms alike, and may enable the use of flow diverters in complex cases like bifurcation and ‘blister-like’ aneurysms where existing options are limited as well.
“In the treatment of intracranial aneurysms in the future, I see an increase in the use of flow diversion,” he adds. “If the study is positive, it means we will be able to treat [more] aneurysms with SAPT, so it will be a major change.”
COATING, Pierot states, is not the only research effort currently evaluating HPC in flow diverter treatments. Another RCT with a comparable design is being conducted in Brazil, with final analyses also expected within a similar timeframe, while two single-arm pivotal studies in the USA and China— enrolling 236 and 120 patients, respectively— are seeking to assess the safety and efficacy of WallabyPhenox’s surface modification technology. Pierot feels these studies will all contribute to the overall body of evidence on HPC across a significant collective of patients from around the globe, and help to identify possible factors influencing the occurrence of thromboembolic complications in endovascular aneurysm care.
Closing the conversation, Pierot offers one final message to his peers in the neurointerventional field: “We need more and more evaluation of what we are doing, and of the devices we are using in the treatment of intracranial aneurysms today. WallabyPhenox has designed a proper study to evaluate whether or not we can reduce antiplatelet medication. The only way to answer this question is an RCT, which is a lot more complex than a registry study, and we have to acknowledge the big effort WallabyPhenox has made to do that. We also have to acknowledge participating centres contributing to the recruitment of patients in France, Germany, Israel, Italy, Slovakia, Switzerland and the UK.
“It’s important—not only for the company, not only for the physicians but, most importantly, for the patients. If the study is positive in favour of the flow diverter with SAPT, we will potentially reduce the rate of complications, haemorrhagic or otherwise, and enlarge the indication for efficacious treatment. This will be a great success for the patient.”
