Abstract
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.
| Original language | English |
|---|---|
| Article number | neurintsurg-2022-018998 |
| Pages (from-to) | E54-E59 |
| Journal | Journal of NeuroInterventional Surgery |
| Volume | 15 |
| Issue number | e1 |
| Early online date | 13 Jul 2022 |
| DOIs | |
| Publication status | Published - 1 Sept 2023 |
Bibliographical note
Funding Information:The MR CLEAN-NO IV trial was funded through the CONTRAST consortium, which acknowledges the support from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation (CVON2015-01: CONTRAST), and from the Brain Foundation Netherlands (HA2015.01.06). The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships (LSHM17016). This work was funded in part through unrestricted funding by Stryker, Medtronic and Cerenovus. The funding sources were not involved in study design, monitoring, data collection, statistical analyses, interpretation of results, or manuscript writing.
Funding Information:
WHvZ reports speaker fees from Cerenovus, Stryker European Operations BV and NicoLab, paid to institution. DWJD reports grants for research from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra, Stryker European Operations BV, Medtronic, Thrombolytic Science and Cerenovus, all paid to institution. YBWEMR is a minor shareholder of Nico.lab. JMC received unrelated research support from The Netherlands Organisation for Health Research and Development, Dr C J Vaillant Foundation, Bayer, Boehringer, Portola. All fees were paid to his employer. CBLMM reports grants from TWIN Foundation, related to MR CLEAN Registry, paid to institution, and unrelated grants from CVON/Dutch Heart Foundation, European Commission, Dutch Health Evaluation Program, Stryker (all paid to institution), shareholder Nico-lab. BJE reports grants from Health Holland Top Sector Life Sciences & Health as well as from the Leading the Change Program (The Netherlands Organization for Health Research and Development), both paid to institution. NLC reports an honorarium for a short presentation at the American Academy of Neurology 2022. The other authors report no conflicts.
Publisher Copyright:
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