Clinical re-evaluation of removing blood stasis therapy in treating acute intracerebral hemorrhage safety and efficacy: a protocol for a randomized, controlled, multicenter study (CRRICH Trial)

Liling Zeng, Jianwen Guo, Jing Wang, Qixin Zhang, Haijun Li, Rongming Lin, Liling Zeng, Jianwen Guo, Jing Wang, Qixin Zhang, Haijun Li, Rongming Lin

Abstract

Background: Hypertensive intracerebral hemorrhage (HICH) is one of the most devastating forms of stroke. Currently, no specific therapies for HICH except general medical care. However, in China, medicine of promoting blood circulation (PBC) and removing blood stasis (RBS) are widely and efficiently used to treat HICH and become a potentially effective treatment for the secondary effects of HICH to alleviate brain injury, accelerate neuronal recovery, and improve the prognosis. In order to evaluate the safety and effect of PBC and RBS herbal drugs, we design a prospective, randomized, open, double-blind controlled clinical trial on the hematoma enlargement in HICH patients treating with PBC and RBS herbal medicine within 6 h time window from the symptom onset.

Methods/design: A multicenter, three-group, prospective, randomized, double-blinded and placebo-controlled clinical trial. Patients aged 18 or older with HICH confirmed by CT scan within 6 h from the onset are included. 360 patients will be randomized to 3 groups (PBC & RBS & Placebo) within 6 h of ictus. Stratified block randomization is undertaken using a sequentially numbered and opaque envelope. All subjects must take medicine within 6 h of ictus and have another CT scan at about 24 h to confirm hematoma expansion. A postal questionnaire to the patients to evaluate their recorvery at 3 months. Primary outcome is the percent change in the volume of hematoma at 24 h. Secondary outcomes include: mortality, disability, serious adverse events, etc.

Conclusions: The CRRICH Trial is expected to confirm the safety and effect of acute intracerebral hemorrhage treated within 6 h of ictus with "RBS" therapy and to determine whether the traditional therapy can cause hematoma growth after intracerebral hemorrhage.

Discussions: This is the first prospective, multicenter, randomized, placebo-controlled clinical trial to investigate herbal medicine whether can induce the incidence of hematoma enlargement of AICH patient within the 6 h time window from onset. We need the data to keep the herbal clinical usage safety. Trial registration clinicaltrials.gov: NCT01918722.

Keywords: Clinical trial; Intracerebral hemorrhage; Promoting blood circulation; Removing blood stasis; Traditional Chinese medicine.

Figures

Fig. 1
Fig. 1
Study design diagram. CT computed tomography, CTA computed tomography angiography, NIHSS National Institutes of Health Stroke Scale, mRS modified Rankin Scale, BI Barthel Index, GCS Glasgow Coma Scale

References

    1. Chinese Pharmacopoeia Commission (2010) The pharmacopoeia of the People’s Republic of China, vol. 1. Chemical Industry Press, Beijing, pp 141, 260
    1. Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006;66(8):1175–1181. doi: 10.1212/01.wnl.0000208408.98482.99.
    1. Fan Y, Jin MW. The influence of Liangxuetongyu oral solution on early rehabilitation of hypertensive cerebral hemorrhage. Chin J Integr Tradit West Med. 2000;20:138–140.
    1. Guo J, He Y, Chen S. Clinical study on the therapeutic time window of acute intracerebral hemorrhage treated with herbal composition of Zhongfengxingnao taken orally. Chin J cerebrovasc Dis. 2005;2(6):255–259.
    1. He D, Liu QR, Zhao JX. Therapeutic efficacy of Xueshuantong injection on patients with acute intracerebral hemorrhage in early stage. Chin J Integr Tradit West Med Intensive Crit Care. 2002;9:27–29.
    1. Huang JL, Li YH, Lin ZP. Therapeutic efficacy of stereotactic microsurgery combined with therapy of inducing resuscitation, activating blood and promoting diuresis in treating severe cerebellopontine hemorrhage. J Guangzhou Univ Tradit Chin Med. 2010;27:445–448.
    1. Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke. 1996;27(10):1783–1787. doi: 10.1161/01.STR.27.10.1783.
    1. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27(8):1304–1305. doi: 10.1161/01.STR.27.8.1304.
    1. Li W. Discussion of early use promoting blood circulation and removing blood stasis herbal medicine. Chin J Basic Med Tradit Chin Med. 2003;05:58–59.
    1. Li HQ, Wei JJ, Xia W, et al. Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis. Acta Pharmacol Sin. 2015;36(6):659–675. doi: 10.1038/aps.2014.139.
    1. Lim JK, Hwang HS, Cho BM, et al. Multivariate analysis of risk factors of hematoma expansion in spontaneous intracerebral hemorrhage. Surg Neurol. 2008;69(1):40–45. doi: 10.1016/j.surneu.2007.07.025.
    1. Liu L, Duan JA, Tang Y, Guo J, Yang N, Ma H, Shi X. Taoren–Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation. J Ethnopharmacol. 2012;139(2):381–387. doi: 10.1016/j.jep.2011.11.016.
    1. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127–2137. doi: 10.1056/NEJMoa0707534.
    1. Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382(9890):397–408. doi: 10.1016/S0140-6736(13)60986-1.
    1. Morgenstern LB, Hemphill JC, 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41(9):2108–2129. doi: 10.1161/STR.0b013e3181ec611b.
    1. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632–1644. doi: 10.1016/S0140-6736(09)60371-8.
    1. Roach ESGMR, Adams RBJ, Daniels SDG, Ferriero DJBV, Kirkham FJSRM, Smith ER. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registr. Stroke. 2005;36:934–937. doi: 10.1161/01.STR.0000160756.72109.95.
    1. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9(2):167–176. doi: 10.1016/S1474-4422(09)70340-0.
    1. Wang YQ, Shi Q, Wang WP (2013) Clinical study of Xuefuzhuyu decoction on hypertensive intracerebral hemorrhage. J Emerg Tradit Chin Med 22:1686–167, 1689 (Chinese)
    1. Wanzhng Y, Zhilan Z, Ming Z, et al. once again on bleeding after cerebral hemorrhage and the time window for therapy of “promoting blood circulation and removing blood stasis”. Chin J Integr Med Cardio Cerebrovasc Dis. 2004;11:662–665.
    1. Xu Y, Guo J, Liu X, et al. Can herbal medicine cause hematoma enlargement of hypertensive intracerebral hemorrhage within 24 hrs time window? A retrospective study of 256 cases from a single center in China. Evid Based Complement Altern Med. 2015;10(8):1155–1158.

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