ABSTRACT NUMBER: ESOC2026LT15 LT15 - SAFETY AND EFFICACY OF RECOMBINANT HUMAN DNASE1 (DORNASE ALFA) AS AN ADJUVANT THROMBOLYTIC IN LARGE VESSEL ISCHAEMIC STROKE: THE EXTEND-IA DNASE CLINICAL TRIAL

Abstract Background and aims Rates of early reperfusion with intravenous fibrinolytics in large vessel ischaemic stroke remain suboptimal. Dornase alfa (DNase1) has no role in physiological haemostasis but accelerates thrombolysis ex vivo through degradation of extracellular DNA in neutrophil extracellular traps, a key structural component of thrombus. We hypothesised that intravenous dornase, combined with standard care thrombolytic, would increase reperfusion at initial angiography pre-EVT in patients with ischaemic stroke due to large vessel occlusion. Methods EXTEND-IA DNase (ClinicalTrials.gov NCT05203224) was an umbrella Bayesian optimal phase 2 study in which patients with ischaemic stroke due to large vessel occlusion aged>18 and receiving standard care thrombolytic received ascending doses of intravenous dornase alfa (Pulmozyme, Roche) 0.125-1mg/kg. Up to 100 patients could be recruited at each dose with interim futility thresholds every 20 patients, powered for a 10% increase above a 20% objective performance criterion for tenecteplase (10% objective performance criterion for alteplase) defined based on the rate of pre-EVT reperfusion in the EXTEND-IA-TNK trials. The primary outcome was >50% early reperfusion (at initial angiography pre-EVT or 1-2h CT-perfusion), without symptomatic intracerebral haemorrhage. Exploratory outcomes included imaging parameters and day90 modified Rankin scale (mRS) compared to EXTEND-IA-TNK trial outcomes. Results Between May2022-Nov2025, 330 patients were enrolled at 17 Australian sites (n=23 0.125mg/kg, n=126 0.25mg/kg, n=98 0.5mg/kg, n=81 1mg/kg), mean age 72 (sd14.8), median NIHSS score 16 (inter-quartile range 10-21). Reperfusion, safety, imaging and functional outcomes will be available for ESOC2026. Conclusions Dornase alfa has potential as a safe adjuvant thrombolytic agent. Conflict of interest