Clinical trial NCT03546283: Neuroprotectant for Hypertensive Intracerebral Hemorrhage
Official title: Efficacy and Safety of Neuroprotectant Cattle Encephalon Glycoside and Ignotin Injection for Intracerebral Hemorrhage: a Multicenter, Randomized, Double-blinded, Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Lead sponsor: Southwest Hospital, China
Sponsor class: OTHER
First posted: 2018-06-06
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: GOSE at 90 days
timeFrame: 90 days after onset
Secondary outcomes:
measure: GOSE at 30 days
timeFrame: 30 days after onset
measure: Score of mRS at 14days, 30 days and 90 days
timeFrame: 14 days, 30 days and 90 days after onset
measure: Score of NIHSS at 14days, 30 days and 90 days
timeFrame: 14 days, 30 days and 90 days after onset
measure: Score of Barthel Index at 14days, 30 days and 90 days
timeFrame: 14 days, 30 days and 90 days after onset
measure: Complications
timeFrame: within 90 days after onset
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Department of Neurosurgery , Southwest Hospital, Third Military Medical University,
state: Chongqing
Study officials:
References: