Efficacy and Safety of Calculus Bovis Sativus (CBS) for Intracerebral Hemorrhage(CBSinICH)

Tongji Hospital

Status: Not yet enrolling

Conditions: Intracerebral Hemorrhage; Brain Hemorrhage

Treatments: Drug: Natural Calculus Bovis(NCB); Drug: Calculus bovis sativus (CBS)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07080632

CBSinICH

Details and patient eligibility

About

The most common cause of death for Chinese patients is intracerebral hemorrhage(ICH), particularly cerebral infarction. It places a heavy burden on people, families, and society as a whole and poses considerable risks of death and disability. The disease is difficult to identify, and is frequently detected only after it progresses to the point of vascular cognitive dysfunction. The primary ischemia necrosis of brain nerve cells and the activation of inflammatory cells are their pathologic processes.

According to historical Chinese medical documents, bezoar possesses properties that can help prevent seizures, treat strokes, enhance cognitive function and mental well-being, and stimulate alertness. Calculus Bovis Sativus (CBS) is the most authentic formulation of bezoar ingredients compared to other bezoar products. It has received approval from the China Food and Drug Administration for the essential treatment of comatose patients. CBS consists of three primary constituents: bilirubin, bile acids, and taurine. Scientific evidence has demonstrated that all of these components possess anti-inflammatory, antioxidant, and neuroprotective properties.

The investigators' objective is to carry out an investigator-initiated clinical study to assess the efficacy of orally administered CBS in treating intracerebral hemorrhag diseases in humans.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. The subject and/or their legal guardian(s) must have full legal capacity, fully understand the purpose, significance, methodology, potential risks, possible adverse effects, types of personal data collected, scope of use, processing methods, retention period, and other relevant information regarding this study. Consent must be given voluntarily.This study will strictly comply with the Personal Information Protection Law, Data Security Law, and other applicable laws/regulations, implementing necessary measures to ensure data security and prevent leakage, tampering, or loss.Upon consent, subjects/guardians authorize the research institution to lawfully process relevant health data, including but not limited to storage, analysis, and statistical use.The institution will strictly limit the scope of personal data usage; no additional purposes will be pursued without separate consent.Subjects/guardians retain the right to access, copy, correct, or delete their data, withdraw consent, or request explanations from the institution.All personal data processing will adhere to legal requirements, ensuring legitimacy, justification, and necessity.

2. Male or female, aged 18-80 years (inclusive) at the time of providing informed nsent.

3. All sexually active participants (male and female of reproductive potential) must use effective contraception during the study and for at least 6 months after the last dose of the investigational treatment.Participants must not donate sperm or eggs during the study or for 6 months post-treatment.

4. Confirmed diagnosis meeting the following criteria:

   1. Hypertensive ICH per Diagnostic Criteria for Spontaneous Intracerebral Hemorrhage in Adults , verified by cranial CT.
   2. Traditional Chinese Medicine (TCM) diagnostic criteria (per Stroke Diagnosis and Efficacy Evaluation Standards by the National TCM Administration's Emergency Research Collaboration Group for Encephalopathy):Primary symptoms: Hemiplegia, impaired consciousness, slurred speech/mutism, sensory deficits, facial deviation.Secondary symptoms: Headache, dizziness, pupillary changes, dysphagia, gaze palsy, ataxia.Diagnosis: ≥2 primary symptoms or 1 primary + 2 secondary symptoms, combined with onset context, predisposing factors, prodromal signs, and age. Imaging may substitute for clinical criteria if insufficient.
   3. Hemorrhage volume: 5-10 mL.
   4. Clinical presentation: Impaired consciousness or significant neurological deficits.
   5. Exclusion: No respiratory failure.

5. Neurological examinations must demonstrate stability within 30 days prior to baseline (Visit 1).

Exclusion criteria

1. Medical History and Current Health Status

   1. Any clinically significant history of cardiac, endocrine, hematologic, hepatic, immune, infectious, metabolic, renal, pulmonary, neurological, dermatologic, psychiatric, or other major diseases, as determined by the investigator, that would interfere with trial participation.

   2. Presence of any untreated intracranial tumor at baseline (randomization).

   3. Alternative causes of symptoms, including:Cerebral hemorrhage due to hematologic disorders or bleeding diathesis.Subarachnoid hemorrhage secondary to trauma.Vascular abnormalities (e.g., aneurysms, arteriovenous malformations).Traumatic brain injury, CNS infections, septic encephalopathy, metabolic encephalopathy, epileptic disorders, mitochondrial diseases, Klein-Levin syndrome, Creutzfeldt-Jakob disease, rheumatologic disorders, Reyes syndrome, or inborn metabolic errors.

   4. Any major surgery within 4 weeks before baseline, excluding:

      Laparoscopic or minor procedures (defined as those requiring only local anesthesia/conscious sedation, performed outpatient; e.g., toenail surgery, mole excision, wisdom tooth extraction).Exclusion: Thymoma or teratoma resection.

   5. Planned surgery during the study (except minor procedures).

   6. History of severe allergies/anaphylaxis or any hypersensitivity reaction that may be exacerbated by study treatment components.

   7. Current or history of malignancy (including solid tumors and hematologic malignancies), except:Basal cell/squamous cell carcinoma fully excised and cured ≥12 months before screening.Subjects with cancer in remission for >5 years may be included after sponsor approval.

   8. History of gastrointestinal surgery (except appendectomy/cholecystectomy >6 months before screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's, ulcerative colitis), or other clinically significant active GI disorders.

   9. Clinically significant recurrent/active GI symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days before screening, requiring:

      New symptomatic treatment (e.g., GERD medication initiation) or dose adjustments within 90 days.

   10. History of diverticulitis or severe GI abnormalities (e.g., symptomatic diverticulosis) that may increase risks (e.g., perforation).

   11. Blood/plasma/platelet donation (≥1 unit) within 90 days before screening.

   12. Active suicidal ideation within 6 months or suicide attempt within 3 years before screening.

   13. Clinically significant laboratory abnormalities per investigator judgment.

   14. Pregnancy, lactation, or plans to conceive during the study or within 3 months post-treatment.

       Women of childbearing potential must have negative serum/urine pregnancy tests at screening and pre-dose.

   15. Physical/mental conditions compromising safety or efficacy assessments.

   16. Screening/baseline systolic BP >150 mmHg or <90 mmHg after 5-minute rest (one repeat allowed; exclusion if persistent).

   17. Within 3 months before screening:Second-/third-degree AV block, sick sinus syndrome, uncontrolled atrial fibrillation, severe/unstable angina, congestive heart failure, myocardial infarction, or major ECG abnormalities (QTc >450 ms [men] or >470 ms [women; Fridericia correction]).

   18. Planned elective procedures/surgery after ICF signing.

   19. Conditions impairing drug absorption (e.g., gastrectomy).

   20. History of heparin allergy or heparin-induced thrombocytopenia.

   21. Clinically relevant abnormalities in medical history, physical exam, ECG, or lab tests.

2. Infection Risk

   1. HIV infection (positive test/history).
   2. Active hepatitis C (HCV Ab+ with detectable HCV RNA).Allowed: HCV Ab+ with undetectable RNA.
   3. Active hepatitis B (HBsAg+ and/or anti-HBc+).Allowed: Prior natural infection (HBsAg-/anti-HBc+/anti-HBs+) or vaccination (HBsAg-/anti-HBc-/anti-HBs+).
   4. Chronic/severe/recurrent infections (e.g., pneumonia, sepsis) within 90 days before baseline.
   5. TB diagnosis/latent TB (positive IGRA or 2 consecutive tests).
   6. Bacterial/fungal/viral infection symptoms (including URI) within 28 days before baseline Re-screening permitted after successful treatment of localized fungal infections (e.g., candidiasis, tinea).
   7. Infection requiring hospitalization/IV antibiotics within 4 weeks before baseline.
   8. Live/attenuated vaccination within 28 days before baseline or planned during the study.
   9. Contraindications to rescue therapies (rituximab, IVIG, high-dose corticosteroids, IV cyclophosphamide).
   10. Prior treatments:Total lymphoid irradiation, cladribine, T-cell/TCR vaccines, stem cell transplant (any time).

3. Laboratory Values

   1. Clinically significant abnormal lab results at screening/baseline (investigator discretion).

   2. Hematologic abnormalities at screening:

      • WBC <3.0 × 10³/µL
      • ANC <2.0 × 10³/µL
      • Lymphocytes <0.5 × 10³/µL
      • Platelets <100 × 10³/µL
      • ALT/AST/GGT ≥3× ULN or bilirubin >2× ULN
      • eGFR ≤60 mL/min/1.73 m²
      • Lymphocytes <LLN

   3. Urinalysis abnormalities at screening:

      • β-2-microglobulin >0.3 μg/mL
      • Albumin/creatinine ratio >22.6 mg/mmol

4. Other

   1. Prior participation in this study.
   2. Blood donation (≥1 unit) within 90 days, plasma within 1 week, or platelets within 6 weeks before screening.
   3. Alcohol/drug abuse within the past year (investigator-determined).
   4. Pregnancy, lactation, or plans to conceive/breastfeed during the study or within 30 days post-treatment.
   5. Current or prior (within 90 days) participation in another clinical trial.
   6. Clinically significant suicidal ideation/behavior within 12 months (per C-SSRS).
   7. Inability/unwillingness to comply with protocol requirements.
   8. Severe hearing/visual impairment, language barriers, claustrophobia, or other conditions preventing neuropsychological assessments/MRI.
   9. Any other reason deemed by the investigator/sponsor to preclude enrollment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

CBS therapy, CBS dosage: 300mg per day from day 1 to day 7, in ICH cohort

Experimental group

Description:

Subjects in ICH cohort of this arm will receive general therapy plus CBS.

Treatment:

Drug: Calculus bovis sativus (CBS)

NCB therapy,NCB dosage: 300mg per day from day 1 to day 7, in ICH cohort

Experimental group

Description:

Subjects in ICH cohort of this arm will receive general therapy plus NCB.

Treatment:

Drug: Natural Calculus Bovis(NCB)