Neuroprotectant for Hypertensive Intracerebral Hemorrhage

Intracerebral Hemorrhage Clinical Trial

Official title:

Efficacy and Safety of Neuroprotectant Cattle Encephalon Glycoside and Ignotin Injection for Intracerebral Hemorrhage: a Multicenter, Randomized, Double-blinded, Placebo-controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03546283
• Other study ID #: Neurosurg 04
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 15, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: June 2018
• Source: Southwest Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cattle encephalon glycoside and ignotin Cattle encephalon glycoside and ignotin (CEGI) injection (drug approval H22025046; Jilin Sihuan Pharmaceutical Co. LTD., Jilin, People's Republic of China) is a compound preparation of muscle extract from healthy rabbits and cattle brain gangliosides, which was approved by the Chinese Food and Drug Administration in 2011 and was commonly used as neuroprotectant in the treatment of central and peripheral nerve injuries in China. To evaluate the safety and efficacy of CEGI in treatment of Hypertensive intracerebral hemorrhage, we designed this study.

Description:

Hypertensive intracerebral hemorrhage (HICH) is a type of stroke that is caused by hypertension-induced intracranial arterial, venous, and capillary ruptures. In recent years, the incidence of HICH has become higher, which has exposed society greatly to heavy social and economic burdens. Therefore it is necessary to find therapeutic strategies. ICH causes primary white matter injury by direct mechanical compression and hematoma expansion, and then it induces secondary injury through toxic product from the blood out of the vessel. The inflammatory response that follows ICH also contributes to the white matter injury. Additionally, post-ICH complications that include cortical thinning, cerebral edema, and hydrocephalus further aggravate the subcortical white matter damage.

The complex injury mechanisms that follow ICH implies that a multi-target neuroprotective agent might be able to achieve better neuroprotective effects than current single-agent neuroprotective therapies.

Cattle encephalon glycoside and ignotin Cattle encephalon glycoside and ignotin (CEGI) injection (drug approval H22025046; Jilin Sihuan Pharmaceutical Co. LTD., Jilin, People's Republic of China) is a multi-target neuroprotective agent that includes polypeptides, various gangliosides, free amino acids and nucleic acids, which were extracted from muscle tissue of healthy rabbits and cattle brain gangliosides, and was approved by the Chinese Food and Drug Administration in 2011, commonly used as neuroprotectant in the treatment of central and peripheral nerve injuries in China.

It has been proven by basic research that CEGI treatment significantly alleviated the neurobehavioral dysfunction, promoted hematoma absorption, effectively up-regulated MBP/MAP-2 expression, and ameliorated white matter fiber damage [1]. CEGI was frequently used in the treatment of intracerebral hemorrhage, yet there is still a lack of high quality study to demonstrate its clinical efficacy. To achieve more clinical evidence of CEGI in treatment of Hypertensive intracerebral hemorrhage, we designed this study to further evaluate the efficacy and safety of CEGI in the treatment of Hypertensive intracerebral hemorrhage.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 422
• Est. completion date: December 31, 2020
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Individuals aged 18-75 years;

2. Newly diagnosed hypertensive intracerebral hemorrhage, bleeding position localizes in Basal ganglia and bleeding volume is within 25-50ml evaluated by head CT, and the hemorrhage does not break into lateral ventricle;

3. Obvious neurological dysfunction after onset, Glasco Comma Scale evaluation between 5-14, or NIHSS above 6, but without signs of cerebral hernia.

4. Enrolled within 72 hours after onset, and CT examination shows no hematomas expansion within 6 hours or above after diagnostic CT (hematoma expansion = 5ml);

5. Written informed consent can be obtained.

Exclusion Criteria:

1. Diagnosed with intracerebral hemorrhage caused by aneurysm, brain tumor, trauma, cerebral parasitic disease, cerebrovascular malformation, moyamoya disease, cerebral arteritis, hematological diseases, or metabolic disorders;

2. Patients whose hematoma is unstable or progress leading to increased intracranial pressure;

3. Ever diagnosed with subarachnoid hemorrhage and ischemic stroke;

4. Ever received anticoagulants or antiplatelet drug treatment within one month prior to onset;

5. Abnormal coagulation function (platelet count <100×109/L, INR>1.4);

6. Patients who need operation treatment (including external ventricular drainage);

7. Patients who may suffer from mental or physical diseases that disturb outcome evaluation;

8. blood homocysteine higher than 15µmol/L when admission;

9. Patients who have serious diseases in heart, lung, liver, kidney, endocrine or hemopoietic system;

10. Allergic to protein or peptide;

11. Drug or alcohol addiction;

12. Pregnant women (positive in pregnancy test or lactating women)

13. Participated in other clinical trials within 3 months;

14. Patients considered as not suitable for clinical trials by researchers.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Intracranial Hemorrhage, Hypertensive

Intervention

Drug:
• Placebos
The patients with hypertensive intracerebral hemorrhage will be randomized into giving placebos, the other treatments in this group follow the guidelines on the treatment of hypertensive intracerebral hemorrhage.
• Cattle Encephalon Glycoside and Ignotin
The patients with hypertensive intracerebral hemorrhage will be randomized into giving CEGI, the other treatments in this group follow the guidelines on the treatment of hypertensive intracerebral hemorrhage.

Locations

Country	Name	City	State
China	Department of Neurosurgery , Southwest Hospital, Third Military Medical University,	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Rong Hu, MD

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GOSE at 90 days	Glasgow Outcome Scale Extended at 90 days	90 days after onset
Secondary	GOSE at 30 days	Glasgow Outcome Scale Extended at 30 days	30 days after onset
Secondary	Score of mRS at 14days, 30 days and 90 days	Global functional performance after stroke in terms of mRS at 14 days, 30 Days and 90 Days, respectively: 0 - No symptoms.1- No significant disability. Able to carry out all usual activities, despite some symptoms.2- Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3- Moderate disability. Requires some help, but able to walk unassisted.4- Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5- Severe disability. Requires constant nursing care and attention, bedridden, incontinent.6- Dead.	14 days, 30 days and 90 days after onset
Secondary	Score of NIHSS at 14days, 30 days and 90 days	Global functional performance after stroke in terms of NIH Stroke Scale at 14 Days, 30 Days, and 90 Days, respectively: (0 = best possible, highest number = best possible) in areas of motor control of the arm (0-4), leg (0-4) sensory perception (0-2), language (0-3), limb ataxia (0-2), gaze (0-2), level of consciousness (0-3), level of consciousness -orientation (0-2), level of consciousness -commands (0-2), facial palsy (0-3), visual (0-3), dysarthria (0-2), and extinction (0-2).	14 days, 30 days and 90 days after onset
Secondary	Score of Barthel Index at 14days, 30 days and 90 days	Global functional performance after stroke in terms of Barthel Index (scores 0~100) at 14 Days, 30 Days, and 90 Days, respectively: scores 100 mean good daily living ability; scores above 60 mean mild function disability that can live independently most time; scores between 60~41 mean moderate function disability that need some help in daily life; scores below 20 mean total disability that live helplessly.	14 days, 30 days and 90 days after onset
Secondary	Complications	Complications incidence including epilepsy, hydrocephalus, cerebral infarction, blooding recurrence, pneumonia and gastrointestinal bleeding	within 90 days after onset