DISTAL trial will elucidate non-dominant M2, M3 and PCA occlusions but sparks debate over ‘true clinical question’

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Marios Psychogios presenting at BRAIN 2022

A recent update on the DISTAL randomised controlled trial (RCT)—which was delivered at the Barts Research and Advanced Interventional Neuroradiology (BRAIN) conference (5–8 December 2022, London, UK)—saw attendees discuss the study’s strengths, and how far it could go towards providing much-needed answers on endovascular therapy (EVT) for medium- and distal-vessel occlusion strokes.

Marios Psychogios (University Hospital Basel, Basel, Switzerland), who presented this update and is also the principal investigator (PI) for DISTAL, described it as a “pragmatic trial”, citing the process by which a patient enters the hospital, undergoes imaging and receives best medical therapy (BMT)—meaning there is no delay to the usual standard of care—before being randomised to ‘angio’ or ‘no angio’.

The DISTAL trial is a European, multicentre RCT evaluating the clinical efficacy of EVT in acute ischaemic stroke patients with an isolated medium vessel occlusion (MeVO) or distal vessel occlusion (DVO). Its primary objective is to determine whether these patients experience superior long-term functional outcomes, measured via the modified Rankin Scale (mRS) at 90 days, when treated with EVT plus BMT versus BMT alone. In his presentation, Psychogios also noted that the chosen approach to EVT (aspiration, stent retriever or both) is at the operator’s discretion.

The speaker relayed that—at the time of the BRAIN conference—a total of 74 patients (rising to 93 as of 9 January 2023) had been enrolled across 25 sites but that, with DISTAL initiating new centres “every week”, this number of sites was expected to rise to around 35 by the end of 2022. Psychogios went on to report that the majority of patients have been enrolled in Switzerland, but Germany, Spain, Finland, and, most recently, Belgium have all contributed, with sites in the UK, Israel and Portugal expected to join soon as well. BRAIN conference director Paul Bhogal (Barts Health NHS Trust, London, UK) is set to be named as the national PI for DISTAL in the UK, Psychogios added.

Highlighting some early results on patient demographics, the speaker also reported an average participant age of 75 years, with the trial mainly enrolling older patient thus far, and a median National Institutes of Health Stroke Scale (NIHSS) score of 5 at admission. The trial has enrolled occlusions spanning a variety of locations, he continued, including non-dominant M2s (40%) and M3s (30%) as well as anterior (6%) and posterior (25%) cerebral artery (ACA/PCA) occlusions.

“In the beginning, we had some gender issues, but this has now been equalised to around 50/50 [male/female],” Psychogios said. “We tried to [make it] as easy as possible for you to include patients, and we also did a lot of work on the randomisation tool.”

Here, Psychogios referred to the fact that exact pre-stroke mRS scores are not mandated under the inclusion criteria, and “only three clicks” are required to randomise patients in DISTAL within the acute setting.

Tips and tricks for MeVOs

Following this update on the trial, Psychogios asserted that, as stroke physicians “climb up the mountain” and go more distally within the neurovasculature, they need more tools—adding that the onus is partly on the companies working in this space to prioritise dedicated devices for treating distal occlusions.

DISTAL core team, left to right: Marios Psychogios, Alex Brehm, Luzia Balmer and Urs Fischer

After running through a handful of noteworthy cases he has performed at his centre, the speaker shared his own setup for treating MeVOs and DVOs, and provided the audience with a number of ‘tips and tricks’, such as placing the primary stent retriever distally (two thirds) to the clot—and combining this with a 4Fr or 5Fr aspiration catheter for M2 occlusions, or a 3Fr aspiration catheter for M3 and A2 occlusions.

“I have used most 3mm stent retrievers with a 0.013-inch microcatheter, [which] is available up to a length of 167cm,” Psychogios said. “And, if you use the shorter 3Fr aspiration catheter that is available in Europe [153cm], you do not actually need to do blind mini-pinning.”

Psychogios added that, for thrombectomies in Basel, he and his colleagues prefer a combined approach, and try to create multiple joints to reduce drag and mitigate straightening of the vessels and avulsion of the perforators during the procedure.

“To conclude, mechanical thrombectomy for MeVOs and DVOs is feasible,” he continued. “Of course, we need randomised controlled data, and we are going to get that with the DISTAL trial but also with the other MeVO/DVO trials like ESCAPE-MeVO [in Canada], with the DISTALS trial [in the USA], and with DISCOUNT in France.”

Is including M2s problematic?

In a subsequent discussion, Tommy Andersson (Karolinska University Hospital, Stockholm, Sweden) commended the DISTAL trial and the “great” pragmatic approach it is utilising, but also voiced reservations regarding “one small problem”—the inclusion of M2 occlusions in the trial, as they often represent a “regular case” akin to an M1.

Tommy Andersson

Responding to Andersson’s suggestion that this may “blur the results”, or make them better than they would have been without including M2s, Psychogios admitted he used to have a similar mindset—that treating M2 occlusions is a “no-brainer”—until he began working in Basel in 2019, and was challenged regarding the lack of existing randomised data on EVT for M2s.

“It is nice to live in this interventional bubble where we see the world as it is from our side, but we also have to consider the conservative neurologists’ side at some point, and produce those data,” he added.

“I agree,” Andersson replied, “but, for me, the difference between an LVO [large vessel occlusion] and a MeVO is that LVOs are [all] pretty much the same—regardless of location, you can put them together and you can trust the results. When you talk about distal occlusions, they are so different depending on the area and how distal they are. So, would it not be difficult in the end to analyse the result and get some guidelines based on that?”

While Psychogios conceded that this does pose a challenge, he stated that—by including only co-dominant or non-dominant M2s—DISTAL is excluding the dominant M2s that were included in prior LVO trials and, thus, can concentrate on occlusion locations where no randomised data exist at the moment. He also cited this as one of the reasons why the DISTAL team is looking to join forces with the other groups running DVO trials, potentially providing a larger sample size of patients and paving the way for further subgroup analyses.

Osama Zaidat

Osama Zaidat (Mercy Health St Vincent Medical Center, Toledo, USA) seconded Andersson’s concerns, adding that, despite being a “good” trial, DISTAL may fail to address the true clinical question in this space owing to the enrolment of M2 cases—many of which are “technically easy to do”. Zaidat also pointed out that several prior RCTs have included M2 occlusions too, meaning there is already an abundance of data on ‘good’ M2s.

He went on to opine that “everybody is scared” of tackling the far more complex ‘true distal cases’, despite these being the cases for which answers are genuinely needed.

“But, I think, down the line, the pooled analysis from all the distal trials will give us an answer,” he concluded—a point that Psychogios agreed with.

Speaking to NeuroNews after the conference, Psychogios clarified once more that not all M2s have been included in the DISTAL trial, and the ‘good’ or ‘easy’ ones that Andersson and Zaidat referenced are subject to the study as per its inclusion criteria. DISTAL will only include co-dominant or non-dominant M2s, meaning the superior M2 trunk (usually the non-dominant one) is frequently targeted in DISTAL, as opposed to the inferior trunk that is regularly included in LVO trials.

He further noted that both the European Stroke Organisation (ESO) and American Heart Association (AHA) guidelines do not give a clear recommendation on whether or not to treat M2 occlusion, due to a “paucity of randomised controlled data”. In addition, as things stand, some 25% of patients in the DISTAL trial are enrolled with a PCA occlusion—a stroke type for which “virtually no” randomised data exist. Thus, Psychogios is “convinced the DISTAL trial will provide answers to an important clinical question”.


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