Rongcai Jiang1, Shiguang Zhao2, Renzhi Wang3, Hua Feng4, Jianmin Zhang5, Xingang Li6, Ying Mao7, Xianrui Yuan8, Zhou Fei9, Yuanli Zhao10, Xinguang Yu11, Wai Sang Poon12, Xide Zhu13, Ning Liu14, Dezhi Kang15, Tao Sun16, Baohua Jiao17, Xianzhi Liu18, Rutong Yu19, Junyi Zhang20, Guodong Gao21, Jiehe Hao22, Ning Su23, Gangfeng Yin24, Xingen Zhu25, Yicheng Lu26, Junji Wei3, Jin Hu7, Rong Hu4, Jianrong Li27, Dong Wang1, Huijie Wei1, Ye Tian1, Ping Lei28,29, Jing-Fei Dong30, Jianning Zhang1. 1. Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education in China and Tianjin, Tianjin Neurological Institute, Tianjin, China. 2. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China. 3. Department of Neurosurgery, Peking Union Medical College Hospital, Beijing, China. 4. Department of Neurosurgery, Southwest Hospital, Chongqing, China. 5. Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 6. Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China. 7. Department of Neurosurgery, Huashan Hospital Fudan University, Shanghai, China. 8. Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, China. 9. Department of Neurosurgery, Xijing Hospital, Xian, China. 10. Department of Neurosurgery, Beijing TianTan Hospital, the Capital Medical University, Beijing, China. 11. Department of Neurosurgery, General Hospital of Chinese People's Liberation Army, Beijing, China. 12. Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong. 13. Department of Neurosurgery, Linyi People's Hospital, Linyi, China. 14. Department of Neurosurgery, Jiangsu Provincial Hospital, Nanjing Medical University First Affiliated Hospital, Nanjing, China. 15. Department of Neurosurgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China. 16. Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, China. 17. Department of Neurosurgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China. 18. Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 19. Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. 20. Department of Neurosurgery, Central Hospital of Erdos, Erdos, China. 21. Department of Neurosurgery, Xi'an Tangdu Hospital of the fourth Military Medical University, Xian, China. 22. Department of Neurosurgery, First Affiliated Hospital of Shanxi Medical University, Taiyuan, China. 23. Department of Neurosurgery, Provincial People's Hospital of Inner Mongolia, Huhehot, China. 24. Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China. 25. Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, China. 26. Department of Neurosurgery, Shanghai Changzheng Hospital, Shanghai, China. 27. Department of Neurosurgery, 117th Hospital of Chinese People's Liberation Army, Hangzhou, China. 28. Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, China. 29. Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China. 30. Bloodworks Research Institute, Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle.
Abstract
Importance: Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. Objective: To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. Design, Setting, and Participants: The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. Interventions: Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. Main Outcomes and Measures: The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. Results: One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported. Conclusions and Relevance: Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. Trial Registration: ClinicalTrials.gov Identifier: NCT02024373.
RCT Entities:
Importance: Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. Objective: To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. Design, Setting, and Participants: The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. Interventions: Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. Main Outcomes and Measures: The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. Results: One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported. Conclusions and Relevance: Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. Trial Registration: ClinicalTrials.gov Identifier: NCT02024373.
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