Application of Magnesium-rich Artificial Cerebrospinal Fluid in Aneurysmal Subarachnoid Hemorrhage

NCT ID: NCT04358445

Last Updated: 2022-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2022-07-30

Brief Summary

Aneurysmal subarachnoid hemorrhage (aSAH) is a common type of acute hemorrhagic stroke. One of its complications, cerebral vasospasm (CVS), is the main cause of death and disability, with an incidence of up to 30%-90%. Blood and its metabolites are vital reasons for CVS. Normal saline, as an intraoperative irrigation fluid for the surgery of aneurysm clipping, can induce secondary damage to the brain. In this study, a new type of magnesium-rich artificial cerebrospinal fluid (MACSF) has been designed, which has similar ionic concentration, pH value and osmotic pressure compared with the physiological cerebrospinal fluid. It has been confirmed by animal experiments that MACSF can relieve the hyper-responsiveness of cerebral arteries to ET and 5-HT induced by hemorrhagic CSF from patients with aSAH by down-regulating the expression of ETA, contractile ETB and 5-HT1B receptors in the previous research. Therefore, MACSF may have potential effects on preventing and treating CVS. In this study, we plan to apply MACSF as an intraoperative irrigation fluid for the surgery of aneurysm clipping (MACSF group), which is compared with normal saline (historical control group). To evaluate the effects of MACSF on reducing the incidence of CVS and improving the clinical prognosis of patients with aSAH, the occurrence of CVS within 14 days after aneurysm clipping, NIHSS score, as well as mRS scores at 1, 3 and 6 months after aSAH will be recorded and compared. CVS related biomarkers will be used to evaluate the relationship between the occurrence of CVS and the levels of biomarkers in both CSF and blood samples from MACSF group.

Detailed Description

From now on, participants who meet the inclusion and exclusion criteria in our hospital will be recruited in the intervention group, if they and their relatives are willing to join in the study. For the historical control group, in which patients were treated by aneurysm clipping in Department of Neurosurgery of the First Affiliated Hospital of Xi'an Jiaotong University during the previous nine months, normal saline (0.9% Sodium Chloride Injection) was applied as intraoperative perfusion solution for their operation. For the intervention group, MACSF will be used. (The composition and concentration of MACSF is as follows: Na+: 146.2 mEq/l, K+: 2.7 mEq/l, Mg2+: 4.2 mEq/l, Cl-: 123 mEq/l, HCO3-: 23.2 mEq/l, Glucose: 0.75 g/l. MACSF is prepared by the staff of Pharmacy Intravenous Admixture Services of First Affiliated Hospital of Xi'an Jiaotong University, according to a specific formula in the specific working area. The whole procedure follow the aseptic principles strictly. Fresh-made MACSF will be placed in a specific container and send to the operating room through specific channels.) Then, for the patients who have signed the informed consent, blood (6ml) and CSF (3ml) samples will be collected during and every other day after the surgery for 14 days. The blood samples should be drawn into a non-anticoagulant tube and a heparin anticoagulant tube respectively. All the samples will be transferred to BioBank of the First Affiliated Hospital of Xi'an Jiaotong University in a liquid nitrogen tank. After re-melted in a water bath of 37℃, the CSF and blood samples will be centrifuged at 4℃ for 10min at 2000r/min, and then the supernatant will be collected and stored at -80℃. At the end of this study, the contents of NPY，MMP-9，MIF，TNF-α，Mg2+ and Ca2+in the samples will be detected by ELISA or mass spectrometry. Transcranial Doppler (TCD) will be observed within 14 days after the operation (daily for the first three days and every other day for the following days). CVS will be diagnosed by TCD, the diagnostic criteria will be described later. CT scan of the brain should be done at least once a week and rechecked anytime when necessary. If there is new low-density lesions, delayed cerebral infarction (DCI) will be diagnosed. The prognosis will be assessed at 1, 3 and 6 months after aSAH onset according to modified Rankin Scale (mRS) . Meanwhile, some indicators will be used to evaluate the safety of MACSF application, which incluiding secondary infection, fluctuation of intracranial pressure and hypermagnesemia. The diagnostic criteria and the solutions will be described in the next part.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Historical control group

The patients were treated by aneurysm clipping in our hospital in the previous nine months, and normal saline (0.9% Sodium Chloride Injection) had applied as intraoperative perfusion solution in operation of the historical control group. All of the 35 patients selected should meet the inclusion and exclusion criteria of this study.

Group Type: NO_INTERVENTION

No interventions assigned to this group

MACSF group

Use Magnesium-Rich Artificial Cerebrospinal Fluid (MACSF) in the operation, and the remaining treatments should strictly follow the guidelines as same as the historical control group.

Group Type: EXPERIMENTAL

Magnesium-Rich Artificial Cerebrospinal Fluid

Intervention Type: OTHER

The Magnesium-Rich Artificial Cerebrospinal Fluid (MACSF) is composed of several qualified clinical intravenous injections according to a specific formula, which has similar physical and chemical properties to physiological CSF. MACSF will be freshly made and used. It will be prepared by trained professionals on a specific workbench and sent to the operating room in a special container. Finally, it will be used in the operation by the neurosurgeons. Aseptic principles should be enforced strictly during the whole procedures, including preparation, transportation and application.

Interventions

Magnesium-Rich Artificial Cerebrospinal Fluid

The Magnesium-Rich Artificial Cerebrospinal Fluid (MACSF) is composed of several qualified clinical intravenous injections according to a specific formula, which has similar physical and chemical properties to physiological CSF. MACSF will be freshly made and used. It will be prepared by trained professionals on a specific workbench and sent to the operating room in a special container. Finally, it will be used in the operation by the neurosurgeons. Aseptic principles should be enforced strictly during the whole procedures, including preparation, transportation and application.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patient is between 18 and 80 years of old;
• aSAH is diagnosed by CTA, DSA or other cranial imaging examination;
• Patient is admitted to hospital within 72 hours after aSAH onset;
• Aneurysm is clipped within 36 hours after admission;
• Patient and his/her relatives are informed and agree to accept the above treatment plan.

Exclusion Criteria

• Cause of the SAH is not rupture of an intracranial aneurysm;
• Time from SAH onset to admission is longer than 72 hours;
• Time from admission to surgery is longer than 36 hours;
• The patient dose not choose clipping;
• Patient has other serious diseases, such as heart failure, kidney failure, liver failure, etc;
• Patient or his/her relatives refuse to accept the above research plan.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luo Guogang, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital Xi'an Jiaotong University

Locations

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Han Xiangning

Role: CONTACT

hxiangning@163.com

0086-18392002455

Luo Guogang, doctor

Role: CONTACT

lguogang@163.com

0086-13991974085

Facility Contacts

Guogang Luo, Ph.D.

Role: primary

86-13991974085

References

Cheng Y, Han X, Xie W, Xu G, Bai X, Qi L, Zhang L, Liu R, Dong W, Feng W, Pang C, Zhang W, Liu F, Cao X, Xu Y, Luo G. Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage. Front Neurol. 2024 Mar 28;15:1376216. doi: 10.3389/fneur.2024.1376216. eCollection 2024.

Reference Type: DERIVED

PMID: 38606277 (View on PubMed)

Other Identifiers

XJYFY-2019N28

Identifier Type: -

Identifier Source: org_study_id