Clinical trial NCT04475328: Efficacy and Safety of AngongNiuhuang Pill in Patients With Acute Ischemic Stroke (ANGONG TRIAL)
Official title: Efficacy and Safety of AngongNiuhuang Pill in Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: Acute Ischemic Stroke
AngongNiuhuang Pill
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: AngongNiuhuang pill has obvious effects on the cardiovascular and cerebrovascular diseases. Pharmacological experiments confirmed that AngongNiuhuang pill can protect blood-brain barrier, inhibit capillary permeability, improve the tolerance of cerebral ischemia and hypoxia, reduce oxidative stress injury, thus protecting brain tissue. Clinical studies have also confirmed that AngongNiuhuang pill can increase the GCS score, reduce coma, improve nerve function defect and promote nerve function recovery. The primary purpose of this trial was to evaluate the difference in the volume of cerebral infarction and cerebral edema between Angong Niuhuang pill and placebo in patients with ischemic stroke at 14 days compared with the baseline.

Detailed description: This trial is a prospective, randomized, double-blinded, placebo parallel controlled, multicenter trial. Patients who met the inclusion and exclusion criteria will be randomized 1:1 into two groups after offering informed content: 1) one group will receive AngongNiuhuang pill 1pill qd/day for 5-day; 2) the other group will receive Placebo of AngongNiuhuang pill 1pill qd/day for 5-day. The primary purpose of this trial was to evaluate the difference in the volume of cerebral infarction and cerebral edema between Angong Niuhuang pill and placebo in patients with ischemic stroke at 14 days compared with the baseline. The study was consisted of six visits, including the day of randomization, 2 days, 3-6 days, 7 days (the endap time of the therapy), 14 days, and 90 days (the endap time of the follow-up). Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The period of the trial is from August 2020 to October 2021, and 120 subjects are planned to be recruited from 10 centers in China. All the related investigative organizations and individuals will obey the Declaration of Helsinki and Chinese Guard-cell protoplast (GCP) standard. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study.

Eligibility criteria: Inclusion Criteria:

1. Male or female participates aged 40-80 years.
2. Diagnosis with acute ischemic stroke.
3. Diagnosis with acute cerebral infarctions of internal carotid artery system.
4. 10≤ Baseline NIHSS \<20.
5. Time of onset ≤36h.
6. Provision of informed consent.

Exclusion Criteria:

1. Not suitable for taking this medicine according to the judgement of consulting traditional Chinese medical doctor.
2. Suffering from intracranial tumors, encephalitis, subarachnoid hemorrhage and other brain organic diseases.
3. Patients with hemorrhagic transformation after cerebral infarction.
4. Received or planned to receive endovascular treatment, including thrombectomy, ultra early thrombectomy and stenting.
5. Received or planned to receive decompression craniectomy.
6. With mRS score \>1 before onset of this episode.
7. Participates who cannot tolerate the MRI scans, such as Using a pacemaker or automatic defibrillator or having claustrophobia.
8. With thrombocytopenia (\<100 x10\^9/L), hematologic diseases or other systemic bleeding tendency.
9. With Alanine transaminase or Aspartate aminotransferase \>1.5 times than normal upper limit or Creatinine \>1.5 times than normal upper limit.
10. Allergic to ingredients of AngongNiuhuang pill.
11. Received AngongNiuhuang pill within 1 month.
12. Participates who plan to become pregnant within 3 months, or women of childbearing age with negative pregnancy test but refuse to accept contraception; during pregnancy or lactation.
13. Participates in other clinical trials within 30 days before randomization or currently involved in other clinical trails.
14. Participates with a life expectancy less than 3 months.
15. Incapable to follow this study due to mental illness, cognitive or emotional disorders.
16. Participates are not eligible for this clinical trial as evaluated by the investigators.

Primary outcomes:
measure: Cerebral infarction volume
timeFrame: 14 days
measure: Cerebral edema volume
timeFrame: 14 days
measure: The proportion of the patients with Severity Adverse Events within 90 days of the treatment.
timeFrame: 90 days
Secondary outcomes:
measure: Cerebral infarction volume
timeFrame: 90 days
measure: Cerebral edema volume
timeFrame: 90 days
measure: The proportion of patients with Modified Rankin Scale (mRS) score ≤ 2 point on the Day 14 and 90 of treatment.
timeFrame: 14 days, 90 days
measure: Changes in NIHSS score on Day 14 and 90 of the treatment from baseline.
timeFrame: 14 days, 90 days
measure: Changes in Glasgow Coma Score (GCS) on the Day 7 and 14 of the treatment from baseline.
timeFrame: 7 days, 14 days
measure: Changes of biomarker (hs-CRP)
timeFrame: 7 days
measure: Changes of biomarker (MMP-9)
timeFrame: 7 days
measure: Changes of biomarker (S-100B)
timeFrame: 7 days
measure: Changes of biomarker (NSE)
timeFrame: 7 days
measure: The proportion of the patients with Severity Adverse Events within 7 days of the treatment.
timeFrame: 7 days
measure: Changes in toxicology index including mercury and arsenic on Day 7 of the treatment.
timeFrame: 7 days
measure: The proportion of the patients with Adverse Events within 7 and 90 days of the treatment.
timeFrame: 7 days, 90 days
measure: The proportion of the patients with All-cause mortality within 7 and 90 days of the treatment.
timeFrame: 7 days, 90 days
measure: The proportion of the patients with Combined vascular events within 7 and 90 days of the treatment.
timeFrame: 7 days, 90 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurology,Peking Union Medical College Hospital,Shuaifuyuan 1,Dong Cheng District. Beijing
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hosptial, Chinese Academy of Medical Sciences
name: Bin Peng, MD
role: PRINCIPAL_INVESTIGATOR
References: