By Dr Thomas Meinel

Official Welcome and Large Clinical Trials

Ladies and gentlemen, prepare to be exhilarated! Following an awareness event in the Munich city center, and the selection from an incredible 1808 abstract submission, we witnessed an awe-inspiring “Official Welcome and Large Clinical Trials Session” at the #ESOC2023 European Stroke Organisation Conference in Munich today! It was filled with great clinical trials that are propelling us towards a future of better stroke care. Each trial showcased a remarkable journey of scientific exploration, unveiling secrets that will update patient care, inform future trials and transform the landscape of stroke medicine.

Anticipation grew among the 4137 participants, and the air was charged with excitement. Social media erupted with a symphony of excitement, as the world caught wind of the trials findings. Now, it’s our turn to bask in the glory of these momentous achievements and embrace the opportunities they present.

First up was the RESIST trial, assessing remote ischemic conditioning in patients with acute ischemic stroke presented by Rolf Blauenfeldt (Aarhus, Denmark). This large trial randomized 1500 patients to pre- and in-hospital remote ischemic conditioning in Denmark. The trial was neutral and remote ischemic conditioning was not associated with a favorable shift in the modified Rankin Scale. Although it was safe and feasible in this setting, there were also no subgroups showing a clear benefit.

Next came the TIMELESS trial testing whether tenecteplase (0.25mg/kgKG) was safe and beneficial in the late time window, but imaging evidence of salvageable tissue and a large vessel occlusion. Gregory Albers (California, United States) presented that in the 458 randomized patients, tenecteplase was not associated with a favorable shift in the mRS or good functional outcome (mRS 0-2). This might have been due to the fact that most patients were treated with mechanical thrombectomy with excellent recanalization rates and short delays between administration of tenecteplase and thrombectomy.

Jeroen de Jonge (Utrecht, Netherlands) presented the PRECIOUS trial aimed to prevent complications in stroke patients of higher age. The PRECIOUS trial assessed whether a pharmacological strategy to prevent aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in elderly patients with a moderately severe to severe acute stroke was more effective at reducing the risk of death and improving functional outcome than current clinical practice of waiting until these complications are manifest before initiating treatment. In this large trial was stopped early after randomization of 1493 patients due to lack of funding. There was no effect neither for prophylactic treatment with metoclopramide, ceftriaxone, or paracetamol. This study adds to the body of trials showing that in a setting of a stroke unit environment with close surveillance and early response to fever, dysphagia and infections, prophylactic treatment does not seem to add any benefit.

The ELAN trial presented by Urs Fischer (Basel, Switzerland) aimed to assess the safety and efficacy of beginning oral anticoagulation earlier than currently recommended by guidelines in ischemic stroke patients with atrial fibrillation. In fact, numerically less recurrent events occurred in the earlier treatment group and there were no safety concerns with earlier treatment. This outstanding trial finally brings evidence to this daily dilemma on stroke unit rounding. Given the results, early treatment initiation is probably better and very unlikely to cause harm if imaging selection to determine the infarct size and rule out relevant hemorrhagic complications is used.

The ARCADIA trial presented by Hooman Kamel (New York, United States) wanted to test the hypothesis that apixaban was superior to aspirin for the prevention of recurrent stroke in patients with cryptogenic ischemic stroke and atrial cardiopathy. Atrial cardiopathy was mostly defined based on ECG criteria and NTproBNP. After randomization of over 1000 patients, the DMSB recommended stopping the trial given that there was no signal for neither efficacy nor harm. Hence, the concept of atrial myopathy needs to be either refined or other treatment strategies might be necessary for optimal secondary prevention in this population.

Thalia Field (Vancouver, Canada) presented the results of the SECRET trial. The SECRET trial was an open-label, randomized, controlled, phase II study that assessed the safety and feasibility of rivaroxaban, compared with standard-of-care (heparin with transition to warfarin , or continued low molecular-weight heparin) for cerebral venous thrombosis. The trial demonstrated feasibility and safety of this approach. However, the (underpowered) crude outcomes favoured the  control arm (warfarin or low molecular weight heparin). Hence, a large phase III study is needed to assess whether direct oral anticoagulation is as effective for cerebral venous thrombosis as warfarin or low molecular weight heparin.

Joanna Wardlaw (Edinburgh, United Kingdom) dived into the results of the LACI-2 trial. This Phase IIb trial was a randomised, partial factorial trial, testing cilostazol, isosorbid mononitrate, both, or neither, in 400 patients with lacunar stroke. This trial incorporated also sophisticated cognitive outcomes. The trial demonstrated the feasibility and tolerability of both drugs and the combination therapy of cilostazol, and isosorbid mononitrate. Although Joanna Wardlaw cautioned the audience, that this trial was not formally powered to test superiority, the audience was very excited about a positive effect of the combination therapy on cardiovascular outcomes as well as cognition. The upcoming LACI-3 will finally answer the question, whether we have new options in the toolbox to manage lacunar ischemic stroke.

Leaving the acute treatment and early secondary prevention, Christopher Schwarzbach (Ludwigshafen, Germany) followed with the results of the SANO trial – a cluster randomized trial to enhance outpatient aftercare for stroke patients. Very similar to the INSPIRE-TMS trial, several cardiovascular risk factors could be reduced by the complex aftercare intervention including blood pressure, lipids, nutrition and physical activity. Unfortunately, this did not translate into a benefit in clinical outcomes, although the intervention group did numerically better.

Last but not least was the RESTORE study presented by PN Sylaja (Thiruvananthapuram, India). This trial assessed whether Ayurvedic rehabilitative treatment was superior to similar duration conventional physiotherapy in improving the sensorimotor recovery of patients with ischemic stroke at 90 days after enrollment measured by the Fugl-Meyer Score. The trial was neutral without benefit for upper limb motor function with Ayurvedic rehabilitative treatment.

Those exciting and guideline changing trials set the 2023 edition of ESOC off to a great start on Wednesday 24th May in Munich, Germany! So, let us embrace these findings with open hearts and curious minds, for they have unlocked novel possibilities. As we leave this session, let us carry the flame of innovation and passion for clinical trials within us, fueling our pursuit of excellence. #ESOC2023 – the voice of stroke in Europe (and beyond) continues to shape the future of stroke medicine and make a lasting impact on the lives of countless individuals.