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Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial

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Abstract

Objective

To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS).

Methods

A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (灯盏细辛注射液, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment.

Results

Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05).

Conclusions

HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608)

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Acknowledgment

We would like to thank all the patients and their families who participated in this study.

Author information

Authors and Affiliations

  1. The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Ming-zhe Hu

  2. Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Zi-yi Zhou & Ye-feng Cai

  3. Department of Acupuncture and Moxibustion, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China

    Zhong-yu Zhou

  4. Department of Neurology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530011, China

    Hui Lu

  5. Department of Neurology, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, 510095, China

    Min Gao

  6. Department of Traditional Chinese Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China

    Long-min Liu

  7. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China

    Hai-qing Song

  8. Department of Traditional Chinese Medicine, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361001, China

    An-ji Lin

  9. Department of Acupuncture and Moxibustion, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, 410005, China

    Qing-ming Wu

  10. Department of Neurology, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, China

    Hong-fei Zhou

  11. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Lei Li

  12. Youcare Pharmaceutical Group Dingcheng Branch, Beijing, 100176, China

    Xia Wang

Authors
  1. Ming-zhe Hu
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  2. Zi-yi Zhou
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  4. Hui Lu
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  7. Hai-qing Song
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  8. An-ji Lin
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  10. Hong-fei Zhou
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  11. Lei Li
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  12. Xia Wang
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  13. Ye-feng Cai
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Contributions

Cai YF proposed the study concepts, designed the study. Zhou ZHY, Lu H, Gao M, Liu LM, Song HQ, Lin AJ, Wu QM and Zhou HF collected the data. Hu MZ and Zhou ZY wrote the manuscript. Wang X participated in quality control and data management. Li L analyzed and interpreted the data. All the authors participated in the clinical studies, acquired the data and approved the final manuscript.

Corresponding author

Correspondence to Ye-feng Cai.

Ethics declarations

This work was supported by the Guangzhou Youcare Biopharmaceutical Co. Ltd. The funding body was not involved in study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The authors declare that there is no conflict of interest regarding the publication of this paper.

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Hu, Mz., Zhou, Zy., Zhou, Zy. et al. Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial. Chin. J. Integr. Med. 26, 420–427 (2020). https://doi.org/10.1007/s11655-020-3094-7

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  • DOI: https://doi.org/10.1007/s11655-020-3094-7

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