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Tenecteplase Plus Butyphthalide for Stroke Within 4.5–6 Hours of Onset (EXIT-BT): a Phase 2 Study

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Abstract

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.

Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

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Data Availability

Request for data collected for the study can be made to the corresponding author and will be considered on reasonable request.

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Acknowledgements

We thank the investigators and research staff (Appendix 1) at the participating sites, members of the trial steering and data monitoring committees (appendix 1). We also thank the participants, their families and friends.

Funding

This study was funded by grants from the Science and Technology Project Plan of Liao Ning Province (2019JH2/10300027; 2022JH2/101500020).

Author information

Authors and Affiliations

  1. Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China

    Hui-Sheng Chen, Ming-Rui Chen, Yu Cui & Xin-Yu Shen

  2. Department of Neurology, General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group, Fushun, China

    Hong Zhang

  3. Department of Neurology, Linghai Dalinghe Hospital, Jinzhou, China

    Jiang Lu

  4. Department of Neurology, Anshan Changda Hospital, Anshan, China

    Li-Wei Zhao

  5. Department of Neurology, General Hospital of Fuxin Mining Bureau of Liaoning Health Industry Group, Fuxin, China

    Ying-Jie Duan

  6. Department of Neurology, Donggang Central Hospital, Donggang, China

    Jing Li

  7. Department of Neurology, Tieling County Central Hospital, Tieling, China

    Ya-Mei Wang

  8. Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

    Lian-Qiu Min

  9. Department of Neurology, Dandong People’s Hospital, Dandong, China

    Li-Hong Zhao

  10. Department of Neurology, Dandong First Hospital, Dandong, China

    Li-Shu Wan

  11. Department of Neurology, Xiuyan County Central People’s Hospital, Anshan, China

    Zai-Hui Zhang

  12. Department of Neurology, Radiology, Boston Medical Center, Boston, Massachusetts, USA

    Thanh N. Nguyen

Authors
  1. Hui-Sheng Chen
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  2. Ming-Rui Chen
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  3. Yu Cui
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  5. Hong Zhang
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  14. Zai-Hui Zhang
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  15. Thanh N. Nguyen
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Contributions

H.S.C. designed the study and wrote the manuscript. M.R.C., X.Y.S. and Y.C. analysed the data. H.Z., J.L., L.W.Z., Y.J.D., J.L., Y.M.W., L.Q.M., L.H.Z., L.S.W., Z.H.Z. participated in data collection and contributed to writing the paper. T.N.N. critically revised the manuscript.

Corresponding author

Correspondence to Hui-Sheng Chen.

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The date the registration submitted to the registry: January 12, 2022

The date of first patient enrollment: February 22 2022

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Chen, HS., Chen, MR., Cui, Y. et al. Tenecteplase Plus Butyphthalide for Stroke Within 4.5–6 Hours of Onset (EXIT-BT): a Phase 2 Study. Transl. Stroke Res. (2024). https://doi.org/10.1007/s12975-024-01231-2

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