APEX-STROKE CALM-ICH Domain

NCT07752719 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: APEX-STROKE CALM-ICH DOMAIN
• Study Type: interventional
• Target: 1,100
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this domain of APEX-STROKE, participants with acute intracerebral hemorrhage (ICH) who meet the eligibility criteria for this domain will be randomized in a 1:1 ratio to receive either Angong Niuhuang pills (ANP) or matching placebo, both in addition to guideline-based standard care. The matching placebo is the control condition and is not counted as a domain intervention.

• Intervention: Angong Niuhuang pills (ANP) in addition to guideline-based standard care. ANP should be initiated as soon as possible after randomization in the ambulance or emergency department setting, with subsequent treatment continued for a total of 14 days according to the domain-specific intervention schedule.
• Control condition: matching placebo in addition to guideline-based standard care.

Conditions

Stroke; Intracerebral Hemorrhage

Outcome Measures

Primary Outcomes (1)

• modified Rankin scale (mRS) scores

  The modified Rankin Scale (mRS) is a 7-point ordinal scale assessing global disability and functional dependence after stroke, ranging from 0 (no symptoms) to 6 (death). Intermediate scores indicate increasing severity: 1, no significant disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; 5, severe disability. The primary analysis will use the ordinal distribution of scores across all 7 levels; lower scores indicate better functional outcome.

  180 days

Secondary Outcomes (6)

• Hematoma volume

  24 hours

• Hematoma Expansion at 24 Hours

  24 hours

• NIHSS score

  24 hours and 7 day

• Mortality

  180 days

• Favorable functional outcome (mRS 0-2 and mRS 0-3)

  180 days

Other Outcomes (2)

• Incidence of Serious Adverse Events

  From randomization through 180 days after randomization

• Incidence of Adverse Events of Special Interest

  From randomization through 180 days after randomization

Study Arms (2)

Early Angong Niuhuang Pill (ANP) treatment

EXPERIMENTAL

Participants in this arm receive early treatment with ANP Within 6 hours of onset.

Drug: Angong Niuhuang Pills (ANP)

Placebo

PLACEBO COMPARATOR

Participants in this arm will not receive ANP and will receive a matching placebo.

Drug: Placebo

Interventions

Placebo DRUG

Matching placebo, identical to Angong Niuhuang pills (ANP) in appearance, smell, taste, dosing schedule, and treatment duration (14 days total). Contains inactive excipients only and is indistinguishable from active treatment to participants, treating teams, outcome assessors, and trial personnel.

Placebo

Angong Niuhuang Pills (ANP) DRUG

Angong Niuhuang pills (ANP), a Traditional Chinese Medicine formulation supplied as 3 g pills, administered in addition to guideline-based standard care. Awake participants receive one pill orally as soon as possible after randomization. Unconscious participants receive a suspension prepared by removing the pill shell and grinding it with 15 mL room-temperature normal saline (used within 1 hour of preparation): in the ambulance setting, administered onto the tongue in 2-2.5 mL increments every 10 minutes, with the remaining dose given via nasogastric tube after hospital admission; in the emergency department, administered directly via nasogastric tube. After the initial dose, treatment continues as one pill twice daily during week 1 and one pill once daily during week 2, for a total treatment duration of 14 days.

Early Angong Niuhuang Pill (ANP) treatment

Eligibility Criteria

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

You may qualify if:

• In-Hospital Setting
• Age ≥18 years.
• Symptom onset or last known well ≤6 hours before randomization. Intracerebral hemorrhage (ICH) confirmed by brain imaging, with a hematoma volume ≥10 mL.
• National Institutes of Health Stroke Scale (NIHSS) score ≥8.
• Glasgow Coma Scale (GCS) score ≥8.
• Traditional Chinese medicine (TCM) syndrome consistent with internal accumulation of heat-toxin, defined by the presence of at least 2 of the following: high fever, facial flushing, agitation, dry mouth, and rapid pulse.
• No surgery performed at the time of randomization.
• Written informed consent obtained from the participant or their legally authorized representative.
• Prehospital (Ambulance) Setting
• Age ≥18 years.
• Symptom onset or last known well ≤6 hours before randomization.
• Predicted to have ICH by an artificial intelligence-based model.
• FAST score ≥2.
• TCM syndrome consistent with internal accumulation of heat-toxin, defined by the presence of at least 2 of the following: high fever, facial flushing, agitation, dry mouth, and rapid pulse.
• Written informed consent obtained from the participant or their legally authorized representative.

You may not qualify if:

• In-Hospital Setting
• Secondary ICH, including ICH associated with cerebrovascular malformations or other structural abnormalities, brain tumors, head trauma, hemorrhagic transformation of cerebral infarction, or bleeding following thrombolysis or thrombectomy.
• Severe comorbidities that may interfere with study treatment, follow-up, or outcome assessment (e.g., severe heart failure, malignant tumors, chronic obstructive pulmonary disease, or severe pre-existing disability).
• Known allergy to Angong Niuhuang Wan or any of its ingredients.
• Pregnancy or breastfeeding.
• History of severe chronic kidney disease or hepatic failure.
• Very high likelihood of death within 7 days or poor anticipated adherence to study treatment or follow-up.
• Prehospital (Ambulance) Setting
• Blood glucose \<2.8 mmol/L.
• History of head trauma within the previous 7 days.
• History of seizures or seizure-like episodes.
• Severe comorbidities that may interfere with study treatment, follow-up, or outcome assessment (e.g., severe heart failure, malignant tumors, chronic obstructive pulmonary disease, or severe pre-existing disability).
• Known allergy to Angong Niuhuang Wan or any of its ingredients.
• Pregnancy or breastfeeding.
• History of severe chronic kidney disease or hepatic failure.

Sponsors & Collaborators

• Fudan University: lead
• Huashan Hospital: collaborator
• Chinese PLA General Hospital: collaborator
• Beijing University of Chinese Medicine: collaborator
• Hubei College of Traditional Chinese Medicine: collaborator
• Guangdong Provincial Hospital of Traditional Chinese Medicine: collaborator

MeSH Terms

Conditions

Stroke; Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 7, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share