Application of Magnesium-rich Artificial Cerebrospinal Fluid in Subarachnoid Hemorrhage

NCT04819451 | Unknown

• 1 other identifier: XJTU1AF2020LSK-195
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Intracerebral hemorrhage (ICH) is one of the common fatal types of cerebral apoplexy with high mortality and disability rates. Hematoma volume and complications of intracerebral hemorrhage are major predictors of early death and poor prognosis. The hematoma and its metabolites are key therapeutic targets. At present, in order to improve the prognosis of patients, cerebrospinal fluid(CSF) replacement with normal saline(NS) is commonly used in clinical practice to clear the bloody components, which shows a good clinical effect. However, due to the large difference between NS and CSF composition, it is easy to cause secondary injury of brain tissue. Therefore, the replacement of artificial CSF with similar CSF composition will be more effective in reducing the incidence of complications and improve the prognosis of neurological function. The Magnesium-rich Artificial Cerebrospinal Fluid(MACSF) was designed and developed in the early stage of this project which has similar physical and chemical properties to physiological CSF, such as ion species, concentration, the potential of hydrogen (pH) value, and osmotic pressure. Animal experiments had confirmed its safety and effectiveness. In this study, patients with basal ganglia intracerebral hemorrhage ruptured into the ventricle or subarachnoid hemorrhage were stratified randomly divided into MACSF group and NS group. MACSF and NS were used as replacement fluid for lumbar puncture CSF replacement, respectively. By observing and comparing two groups of patients of the Modified Rankin Scale (mRS) on the days14, 30, 60 and 90 after onset; hematoma absorption rate, hemorrhagic CSF removal rate; changes of cerebral autoregulation； incidence of complications, such as acute obstructive hydrocephalus (AOH) and cerebral vasospasm (CVS); the changes of scores and scales about imaging; assessment of neurological function recovery, such as the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Score (GCS) during hospitalization, headache duration and the Visual Analogue Scale (VAS), vomiting duration, duration of meningeal irritant, ICU hospitalization duration, total hospitalization duration; change of CSF and peripheral blood biochemical indicators. The objective is to evaluate MACSF replacement therapy in patients with basal ganglia cerebral hemorrhage broken into ventricles and nonaneurysmal subarachnoid hemorrhage of the influence of absorption rate and prognosis.

Conditions

Intracranial Hemorrhage

Keywords

Intracranial Hemorrhage; Artificial cerebrospinal fluid; Cerebrospinal fluid replacement; Subarachnoid Hemorrhage

Outcome Measures

Primary Outcomes (1)

• The mRS score at 14, 30, 60,90 days after onset

  Assess patients' prognosis by the score of modified Rankin Scale.In the mRS, the lowest score is 0, and the highest score is 5. A score of 0 indicates the patients have no symptoms at all, and a score of 5 indicates the patients have severe disability, bed rest, incontinence, and need for continuous care and attention. In this study, we evaluate patient's outcomes by the following criteria. Favorable outcome was defined as mRS\<3, whereas poor outcome was mRS≥3.

  in the day of 14, 30, 60, 90 days after onset.

Secondary Outcomes (15)

• Clearance rate of hemorrhagic CSF

  Within 30 days after onset.

• The absorption rate of hematoma

  Within 30 days after onset.

• CT imaging: The max-ICH score (max-ICH)

  Within 30 days after onset.

• CT imaging: the IVH score (IVHs)

  Within 30 days after onset.

• CT imaging: the Modified Graeb Score (mGS)

  Within 30 days after onset.

Other Outcomes (3)

• Fluctuation of intracranial pressure(ICP)

  Before each cerebrospinal fluid replacement during the hospitalization.

• Incidence and severity of MACSF-induced infection

  Within 20 days after onset.

• Incidence of hypermagnesemia

  Within 20 days after onset.

Study Arms (2)

MACSF group

EXPERIMENTAL

In the experimental group, patients with intracerebral hemorrhage ruptured into the ventricle and patients with subarachnoid hemorrhage were included in the stratified random method. Use Magnesium-Rich Artificial Cerebrospinal Fluid(MACSF) in the CSF replacement, and the remaining treatments should strictly follow the guidelines as same as the control group. The total amount of replacement was generally 30ml, and the replacement was performed once every 3 days. When the RBC count in CSF is less than 100×10\^6/L, the CSF is considered to be cleared. Cerebrospinal fluid replacement is performed up to four times.

Other: Magnesium-Rich Artificial Cerebrospinal Fluid (MACSF)

NS group

NO INTERVENTION

In the control group, patients with intracerebral hemorrhage ruptured into the ventricle and patients with subarachnoid hemorrhage were included according to the stratified random method. Use the normal saline (0.9% Sodium Chloride Injection) in the CSF replacement, and the remaining treatments should strictly follow the guidelines. The total amount of replacement was generally 30ml, and the replacement was performed once every 3 days. When the RBC count in CSF is less than 100×10\^6/L, the CSF is considered to be cleared. Cerebrospinal fluid replacement is performed up to four times.

Interventions

Magnesium-Rich Artificial Cerebrospinal Fluid (MACSF) 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 patient wards in a special container. Finally, it will be used in the CSF replacement. Aseptic principles should be enforced strictly during the whole procedures, including preparation, transportation and application.

MACSF group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between 18 and 80 years of old;
• Patients with ICH rupture into the ventricle in the primary basal ganglia region or non-aneurysmal subarachnoid hemorrhage confirmed by skull imaging examination;
• Patient is admitted to hospital within 72 hours after onset;
• Informed consent of the patients or their family members, and signed informed consent for CSF replacement treatment.

You may not qualify if:

• Non-spontaneous intracranial hemorrhage;
• Time from onset to admission is longer than 72 hours;
• The patient who needs surgical treatment;
• Contraindication of lumbar puncture, such as: cerebral hernia, severe intracranial hypertension, puncture site inflammation, blood system diseases, etc.;
• 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.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

MeSH Terms

Conditions

Intracranial Hemorrhages; Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Guogang Luo, MD, PHD

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yixin Zhao

CONTACT

0086-15291859063; yihsinchao@163.com

Guogang Luo, Doctor

CONTACT

0086-13991974085; lguogang@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: rospective, interventional, double-blind, completely randomized, stratified controlled clinical trial

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 29, 2021
• Study Start: April 30, 2021
• Primary Completion: January 1, 2024
• Study Completion: February 1, 2024
• Last Updated: June 15, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)