Treatment of chronic subdural hematoma with atorvastatin combined with low-dose dexamethasone: phase II randomized proof-of-concept clinical trial

Dong Wang MD, PhD 1 , 2 , Chuang Gao MD, PhD 1 , 2 , Xin Xu MD, PhD 1 , 2 , Tao Chen PhD 3 , Ye Tian MD, PhD 1 , 2 , Huijie Wei MD 1 , 2 , Shu Zhang PhD 2 , Wei Quan MD, PhD 1 , 2 , Yi Wang MD 1 , 2 , Shuyuan Yue MD 1 , 2 , Zengguang Wang MD, PhD 1 , 2 , Ping Lei MD, PhD 4 , Craig Anderson MD, PhD 5 , Jingfei Dong MD, PhD 6 , Jianning Zhang MD, PhD 1 , 2 , and Rongcai Jiang MD, PhD 1 , 2
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  • 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin;
  • 2 Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in the Central Nervous System, Ministry of Education, Tianjin Medical University, Tianjin Key Laboratory of Injury and Regenerative Medicine of Nervous System, Tianjin Neurological Institute, Tianjin, China;
  • 3 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom;
  • 4 Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China;
  • 5 George Institute China at Peking University Health Science Center China and George Institute for International Health, University of Sydney, Australia; and
  • 6 Bloodworks Research Institute, Bloodworks Northwest and Department of Medicine, University of Washington School of Medicine, Seattle, Washington
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The authors sought to test the hypothesis that adding dexamethasone (DXM) to atorvastatin (ATO) potentiates the effects of ATO on chronic subdural hematoma (CSDH).


Sixty patients with CSDH underwent 5 weeks of treatment with an additional 7-week follow-up. Patients were randomized to receive a 5-week regimen of ATO 20 mg daily or ATO 20 mg daily plus a DXM regimen (ATO+DXM). The 5-week DXM regimen was 2.25 mg daily for 2 consecutive weeks, followed by 0.75 mg twice daily for 2 weeks and 0.75 mg once daily for 1 week. The primary endpoint was hematoma reduction assessed by neuroimaging at baseline and at 5 weeks of follow-up. Secondary outcomes included neurological improvement assessed by using the Markwalder’s Grading Scale and Glasgow Coma Scale (MGS-GCS).


The mean patient age was 66.6 years, and 25% of patients were women. The patients who were treated with ATO+DXM had more obvious hematoma reduction at the 5th week (between-groups difference 18.37 ml; 95% CI 8.17–28.57; p = 0.0005). This reduction started from the 2nd week (14.51 ml; 95% CI 4.31–24.71; p = 0.0056) of treatment and persisted until the 12th week (17.50 ml; 95% CI 7.30–27.70; p = 0.0009). Complete recovery of neurological function (MGS-GCS grade 0) at 5 weeks was achieved in 83.33% and 32.14% of patients in the ATO+DXM and ATO groups, respectively. At the 5th week, patients receiving ATO+DXM had significantly lower levels of T cells and higher levels of regulatory T cells and endothelial progenitor cells in their peripheral blood.


ATO+DXM was more effective than ATO alone in reducing hematoma and improving neurological function in patients with CSDH. These results require further confirmation in a randomized placebo-controlled trial.

Clinical trial registration no.: ChiCTR-IPR-14005573 (

ABBREVIATIONS ADL = activities of daily living; ADL-BI = ADL according to the modified Barthel Index; ATO = atorvastatin; CSDH = chronic subdural hematoma; DXM = dexamethasone; EPC = endothelial progenitor cell; FACS = fluorescence-activated cell sorting; FITC = fluorescein isothiocyanate; GOSE = Glasgow Outcome Scale–Extended; HV = hematoma volume; LOCF = last observation carried forward; MGS-GCS = Markwalder’s Grading Scale and Glasgow Coma Scale; PE = phycoerythrin; Treg = regulatory T cell.

Supplementary Materials

    • pdf Supplementary Tables and Figure (PDF 15.8 MB)

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Contributor Notes

Correspondence Rongcai Jiang: Tianjin Medical University General Hospital, Tianjin, China.

INCLUDE WHEN CITING Published online January 31, 2020; DOI: 10.3171/2019.11.JNS192020.

D.W., C.G., and X.X. contributed equally to this work. J.Z. and R.J. contributed equally to the supervision of this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.


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