Shuxuening Injection for the Prevention of CVS in Patients With aSAH(SXN-CVS)

Subarachnoid Hemorrhage, Aneurysmal Clinical Trial

— SXN-CVS  

Official title:

Shuxuening Injection for the Prevention of Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage -- A Randomized, Double-blind, Placebo-parallel Controlled Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06138353
• Other study ID #: HX-A-2023023
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 24, 2024
• Est. completion date: November 30, 2025

Study information

• Verified date: March 2024
• Source: Beijing Tiantan Hospital
• Contact: Jun Yang, doctoral
• Phone: 010-18911127316
• Email: yangjun4780[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aneurysmal subarachnoid hemorrhage (SAH) is a frequent worldwide cause for stroke with a mortality of around 30%. Worldwide, almost 500 000 patients have aneurysmal SAH annually.An incidence of 2-16 cases of spontaneous SAH per 100 000 person-years was reported in a recent meta-analysis . Surgical treatment of aneurysms is essential in the acute phase of aSAH patients, either by surgical clipping or by endovascular embolization. Although there are many factors that influence the prognosis of patients with aSAH, cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) are the main factors contributing to the high mortality rate (30-40% within 30 days) and poor long-term functional prognosis of patients after aSAH. Cerebral vasospasm (CVS) is defined as focal or diffuse temporary narrowing of vessel diameter due to contraction of smooth muscle in the arterial wall, which can be detected by digital subtraction angiography (DSA), transcranial ultrasound Doppler (TCD), magnetic resonance (MR), and CT angiography (CTA) or visualised during intraoperative.The prevalence of CVS after aSAH is 67% , with symptomatic patients (symptomatic vasospasm) in 30-40% of them and leading to ischaemic events in 10-45% of patients. It usually begins 3-4 days after bleeding, peaks at 7-10 days and finally resolves at around 14-21 days. There is no effective treatment to prevent cerebral vasospasm events.Shuxuening Injection is a sterilized aqueous solution made by extraction of Ginkgo biloba. The study aims to clarify the clinical study of the efficacy and safety of Shuxuening Injection (10ml/branch) for the prophylactic of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage.

Description:

This was a randomized, double-blind, placebo-parallel controlled clinical trial. Patients were randomly divided into 2 groups according to 1:1. Group1: Shuxuening injection treatment group (N1=25): Shuxuening injection (specification: 10ml/branch, Lonch Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days; Group2: Placebo control group (N2=25): Shuxuening injection simulant (0.9% sodium chloride injection, specification: 10ml/cartridge, Kunming Yusi Pharmaceutical Co., Ltd.), 20 ml (2 cartridges) + 5% dextrose injection 250 ml, intravenously once a day, from the first day of postoperative, treatment for 1 course of treatment, for a total of 10-14 days; both groups received the basal treatment. Basic treatment included nimodipine (oral nimodipine, 60 mg, 4 hours/dose), oxygen inhalation,blood pressure and cardiac monitoring, fluid balance and blood glucose management, etc., in accordance with the "2023 American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Management of Patients with Aneurysmal Subarachnoid Haemorrhage". Patients will be classified according to the Hunt-Hess grade, with H-H I-II grade placed in the general ward and III-V grade placed in the intensive care unit(ICU).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. adult patients (> 18 years of age)

2. patients who were diagnosed with aneurysmal subarachnoid hemorrhage

3. the aneurysms were treated by microsurgery clipping or endovascular coiling

4. Time from onset to surgery is less than or equal to 72 hours;

5. no new hemorrhage or new infarction on first postoperative CT;

6. signed informed consent.

Exclusion Criteria:

1. mRS >1 before onset

2. history of microsurgery clipping or endovascular coiling

3. anemia (hemoglobin <10g/dL), thrombocytopenia (platelet count <100×10^9/L), or leukopenia (white blood cell count <3×10^9/L) at randomization

4. patients with chronic liver and kidney dysfunction (including those with alanine aminotransferase (ALT) and aliquot aminotransferase (AST) > 3 times the upper limit of normal, and those with blood creatinine (Scr) > 2 times the upper limit of normal)

5. patients suffering from cardiorespiratory insufficiency disease such as heart failure, severe heart disease, respiratory failure

6. allergy to Shuxuening Injection

7. those who have used Shuxuening Injection before enrolled

8. patients with end-stage disease, those with a life expectancy of less than 3 months

9. women who are prepare for pregnancy in 3 months, pregnant or breastfeeding

10. those who are participating or have participated in other clinical trials within the past 1 month

11. patients are unable to comply with this study due to mental illness, cognitive or emotional disorders, etc. or that the investigator think patients inappropriate for this study

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal

Intervention

Drug:
• Shuxuening injection or placebo
Shuxuening injection treatment group : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Xiaolin Chen, MD

Country where clinical trial is conducted

China, 

References & Publications (9)

Calapai G, Crupi A, Firenzuoli F, Marciano MC, Squadrito F, Inferrera G, Parisi A, Rizzo A, Crisafulli C, Fiore A, Caputi AP. Neuroprotective effects of Ginkgo biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis. Life Sci — View Citation

Dankbaar JW, de Rooij NK, Velthuis BK, Frijns CJ, Rinkel GJ, van der Schaaf IC. Diagnosing delayed cerebral ischemia with different CT modalities in patients with subarachnoid hemorrhage with clinical deterioration. Stroke. 2009 Nov;40(11):3493-8. doi: 10 — View Citation

Geraghty JR, Testai FD. Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: Beyond Vasospasm and Towards a Multifactorial Pathophysiology. Curr Atheroscler Rep. 2017 Oct 23;19(12):50. doi: 10.1007/s11883-017-0690-x. — View Citation

Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017 Feb 11;389(10069):655-666. doi: 10.1016/S0140-6736(16)30668-7. Epub 2016 Sep 13. — View Citation

Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014 Jan;10(1):44-58. doi: 10.1038/nrneurol.2013.246. Epub 2013 Dec 10. — View Citation

Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci. 2008 Jan;73(1):R14-9. doi: 10.1111/j.1750-3841.2007.00597.x. — View Citation

Tulsulkar J, Shah ZA. Ginkgo biloba prevents transient global ischemia-induced delayed hippocampal neuronal death through antioxidant and anti-inflammatory mechanism. Neurochem Int. 2013 Jan;62(2):189-97. doi: 10.1016/j.neuint.2012.11.017. Epub 2012 Dec 7 — View Citation

Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid h — View Citation

Westermaier T, Jauss A, Eriskat J, Kunze E, Roosen K. Acute vasoconstriction: decrease and recovery of cerebral blood flow after various intensities of experimental subarachnoid hemorrhage in rats. J Neurosurg. 2009 May;110(5):996-1002. doi: 10.3171/2008. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	modified Rankin scale(mRS)	modified Rankin scale(mRS) ranged from a minimum of 0 to a maximum of 5, with higher scores representing a worse outcome.	modified Rankin scale(mRS) within 14 days and 90 days
Primary	Number of Participants with cerebral vasospasm(CVS)	The prevalence of CVS after aSAH is 67% , with symptomatic patients (symptomatic vasospasm) in 30-40% of them and leading to ischemic events in 10-45% of patients. It usually begins 3-4 days after rupture bleeding, peaks at 7-10 days and finally resolves at around 14-21 days.	Cerebral vasospasm events within 14 days
Secondary	Rate of Delayed Cerebral Ischemic(DCI)	Delayed cerebral ischemic events within 14 days	Delayed cerebral ischemic events within 14 days