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Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV


Background We assessed whether the treatment effect of intravenous alteplase (IVT) prior to endovascular treatment (EVT) on functional outcome is modified by time metrics.

Methods We used data from all patients included in MR CLEAN-NO IV, a randomized trial of IVT followed by EVT versus EVT alone in patients who presented directly to EVT-capable hospitals. The primary outcome was the modified Rankin Scale score at 90 days. We used ordinal regression with a multiplicative interaction term to assess if the effect of IVT is modified by onset-to-randomization (OTR), onset-to-IV-needle (OTN), door-to-groin (DTG) or needle-to-groin (NTG) times. Secondary outcomes included successful reperfusion (extended Thrombolysis In Cerebral Infarction Scale 2b–3) and symptomatic intracranial hemorrhage (sICH).

Results In 539 included patients (266 allocated to IVT+EVT and 273 to EVT alone), median workflow times were OTR: 93 (IQR 71–145) min; OTN: 98 (IQR 75–156) min; DTG: 64 (IQR 51–78) min; and NTG: 28 (IQR 20–41) min. There was a significant association between worse outcomes and longer time intervals for all metrics except NTG. We found no interaction between any of the time metrics and IVT for the effect on functional outcome (p values for interaction: OTR=0.40, OTN=0.39, DTG=0.61, NTG=0.56). We also did not observe any significant interaction for successful reperfusion or sICH.

Conclusion In MR CLEAN-NO IV, the effect of IVT prior to EVT was not modified by OTR, OTN, DTG or NTG times. Our results do not support the use of these metrics to guide IVT treatment decisions prior to EVT in comprehensive stroke centres.

Trial registration number ISRCTN80619088.

  • stroke
  • thrombectomy
  • thrombolysis

Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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