Early Administration of Angong Niuhuang Pill for Disabling Acute Ischemic Stroke (EAGER Trial)

Acute ischemic stroke is a major cause of death and long-term disability worldwide. Patients presenting with moderate-to-severe neurological deficits remain at substantial risk of poor functional outcomes despite advances in reperfusion therapies and contemporary standard-of-care management. Early neurological protection and limitation of secondary brain injury may therefore represent an important therapeutic strategy in addition to reperfusion and other standard treatments.

Angong Niuhuang Pill is a traditional Chinese medicine preparation that has been used clinically for acute neurological disorders. Preclinical and pharmacological evidence suggests that ANP may exert neuroprotective effects through multiple biological pathways, including attenuation of neuroinflammation, reduction of oxidative stress, preservation of the blood-brain barrier, and mitigation of ischemia-reperfusion injury. These potentially complementary mechanisms may help limit secondary neuronal injury and promote neurological recovery after acute cerebral ischemia. However, the clinical efficacy and safety of early ANP administration in patients with disabling acute ischemic stroke remain insufficiently established, particularly in patients with moderate-to-severe neurological deficits treated within the early phase after stroke onset.

Eligible patients will be adults aged 18 to 80 years with imaging-confirmed acute ischemic stroke involving the anterior circulation, a baseline National Institutes of Health Stroke Scale (NIHSS) score of 10 to 19, symptom onset or last known well within 24 hours before randomization, and a prestroke modified Rankin Scale (mRS) score of 0 to 1. Patients meeting all eligibility criteria will be centrally randomized in a 1:1 ratio using an interactive web response system with study-center stratification and block randomization.

Participants assigned to the intervention group will receive Angong Niuhuang Pill, 3 g once daily for 5 consecutive days, administered orally or through a nasogastric tube. Participants assigned to the control group will receive a matching placebo with the same dose, route of administration, and treatment duration. The placebo is designed to be similar in appearance, odor, taste, and packaging to the active treatment. Both groups will receive standard-of-care management for acute ischemic stroke according to applicable clinical guidelines and investigator judgment.

The primary objective is to determine whether early administration of ANP improves functional outcome at 90 days, as assessed by the proportion of participants achieving functional independence, defined as a modified Rankin Scale score of 0 to 2.

Secondary objectives include evaluation of excellent functional outcome (mRS 0-1) at 90 days, the distribution of mRS scores from 0 to 6 at 90 days, changes in the Barthel Index from baseline to day 90, changes in NIHSS from baseline to day 14 and day 7, the proportion of participants with a decrease in NIHSS score of at least 4 points by day 14, and the incidence of symptomatic intracranial hemorrhage within 7 days according to the European Cooperative Acute Stroke Study III (ECASS III) definition.

Safety will be assessed throughout the 90-day follow-up period, including serious adverse events, all-cause mortality, and changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine from baseline to day 7.

The study will enroll approximately 1,200 participants across multiple clinical centers in China. The treatment period is 5 days, and participants will be followed for 90 days after randomization. The study is designed to provide robust evidence regarding the efficacy and safety of early ANP administration as an adjunctive treatment for patients with disabling acute ischemic stroke.