Chaigui Longmu Ejiao Paste for Ischemic Heart Disease

The mean change in the average number of angina attacks per week from baseline to the end of the 8-week treatment period in patients with ischemic heart disease ; Recorded using electronic patient-reported outcomes (ePRO).

The Seattle Angina Questionnaire (SAQ) is a validated, disease-specific, self-reported instrument that assesses health status in patients with angina due to ischemic heart disease. It measures five domains: Physical Limitation (extent of limitation in physical activity due to angina), Angina Stability (change in angina frequency over the past 4 weeks), Angina Frequency (frequency and burden of angina episodes), Treatment Satisfaction (satisfaction with angina treatment), and Disease Perception/Quality of Life (impact of angina on quality of life). Each domain is scored from 0 to 100, with higher scores indicating better health status (less limitation, fewer symptoms, greater satisfaction, better quality of life).

Change = (Week 4 or Week 8 Score - Baseline Score) for each domain and the total score (overall summary score, if applicable, averaging the relevant domains).

The average number of nitroglycerin tablets (or sublingual sprays) used per week by the participant to relieve angina symptoms. This is a key indicator of angina burden and rescue medication requirement.

The TCM Syndrome Score is a composite system based on the diagnostic criteria for the pattern "Chest Yang Deficiency with Heart Vessel Stasis".

It assesses severity of:

• Primary symptoms (chest oppression/chest pain, palpitations)
• Secondary symptoms (insomnia, aversion to cold, spontaneous sweating, irritability/restlessness of heart and mind) Tongue and pulse are observed but not scored numerically.

Scoring:

• Primary symptoms: 0 (absent), 2 (mild), 4 (moderate), 6 (severe)
• Secondary symptoms: 0 (absent), 1 (mild), 2 (moderate), 3 (severe) Total score = sum of all symptom scores. Higher score = greater severity. Change value

• score at week 4 or 8 - baseline score A lower (more negative) change value indicates greater improvement in the TCM syndrome.

The Hamilton Anxiety Rating Scale (HAM-A) is a clinician-administered, 14-item instrument that assesses the severity of anxiety symptoms. Each item is scored from 0 (none) to 4 (severe), with a total score ranging from 0 to 56 (higher scores indicate greater anxiety severity).

The scale are administered by trained clinicians. Change = (Week 4 or Week 8 total score - Baseline total score) for each scale. Negative changes indicate improvement (reduction) in anxiety symptoms.

The Hamilton Depression Rating Scale (HAMD-24) is a clinician-administered 24-item scale used to assess the severity of depressive symptoms. Most items are scored on a 5-point scale (0 = absent to 4 = very severe), with some items scored on a 3-point scale (0 = absent to 2 = severe). Total score ranges from 0 to approximately 76, with higher scores indicating greater severity of depression.

The scale is administered by trained clinicians. Change = (Week 4 or Week 8 total score - Baseline total score). Negative changes indicate improvement (reduction) in depressive symptoms.

The SF-36 is a validated 36-item self-reported questionnaire that assesses health-related quality of life across 8 domains (scores 0-100, higher = better). The Physical Component Summary (PCS) is a norm-based summary score derived from weighted factor analysis of the 8 domains, standardized to a general population mean of 50 and standard deviation of 10 (higher scores indicate better physical health-related quality of life). Chinese mainland adapted version (validated by Li et al., Zhejiang University, Hangzhou community norms) used. Change = (Week 4 or Week 8 PCS score - Baseline PCS score). Positive changes indicate improvement in physical health-related quality of life. Administered via self-report with guidance from study personnel.

The SF-36 is a validated 36-item self-reported questionnaire that assesses health-related quality of life across 8 domains (scores 0-100, higher = better). The Mental Component Summary (MCS) is a norm-based summary score derived from weighted factor analysis of the 8 domains, standardized to a general population mean of 50 and standard deviation of 10 (higher scores indicate better mental health-related quality of life). Chinese mainland adapted version (validated by Li et al., Zhejiang University, Hangzhou community norms) used. Change = (Week 4 or Week 8 MCS score - Baseline MCS score). Positive changes indicate improvement in mental health-related quality of life. Administered via self-report with guidance from study personnel.

Major Adverse Cardiovascular Events (MACE) is a composite safety endpoint defined as the occurrence of any of the following events during the 8-week treatment period:

Cardiovascular death Non-fatal myocardial infarction (MI) Non-fatal stroke Hospitalization for unstable angina requiring urgent revascularization Other protocol-defined major cardiovascular events (if applicable, e.g., severe heart failure exacerbation or resuscitated cardiac arrest)

The incidence rate is calculated as the proportion of participants experiencing at least one MACE event (number of participants with ≥1 event / total number of participants in the analysis population × 100%). Events are adjudicated by an independent clinical events committee (if applicable) or by the investigator based on clinical records, ECG, biomarkers, and imaging.

This outcome is assessed for safety monitoring and exploratory comparison between treatment arms.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Body temperature (°C) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Pulse rate (beats per minute, bpm) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Respiratory rate (breaths per minute) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.

Vital signs are monitored as a key safety parameter to evaluate the physiological tolerability and potential adverse effects of the investigational treatment.

Blood pressure (systolic and diastolic, mmHg) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) are recorded and reported separately.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Hematology (Blood Routine): Red Blood Cell count (RBC) Unit: ×10¹²/L (Number of red blood cells per liter of blood × 10¹²)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Hematology (Blood Routine): White Blood Cell count (WBC) Unit: ×10⁹/L (Number of white blood cells per liter of blood × 10⁹)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Hematology (Blood Routine): Platelet count (PLT) Unit: ×10⁹/L (Number of platelets per liter of blood × 10⁹)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Hematology (Blood Routine): Hemoglobin (Hb)-Hemoglobin Concentration Unit: g/L (grams per liter) or g/dL

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Liver Function: Alanine Aminotransferase (ALT) Unit: U/L (units per liter)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Liver Function: Aspartate Aminotransferase (AST) Unit: U/L (units per liter)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Liver Function: Total Bilirubin (TBIL) Unit: μmol/L (micromoles per liter)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Liver Function:Alkaline Phosphatase (ALP) Unit: U/L (units per liter)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Renal Function: Serum Creatinine (Scr) Unit: μmol/L (micromoles per liter) or mg/dL

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Urinalysis (Urine Routine): Protein (PRO) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mg/dL, g/L)

All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Urinalysis (Urine Routine): Glucose (GLU) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mmol/L, mg/dL) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Urinalysis (Urine Routine): Erythrocytes (ERY) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment.

Urinalysis (Urine Routine): Leukocytes (LEU) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.

Heart rate (beats per minute) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Used for cardiac safety monitoring. Clinically significant changes are reported as adverse events.

Unit of Measure: beats per minute (bpm)

PR interval (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Assessed as part of cardiac conduction safety evaluation. Clinically significant prolongation is reported as an adverse event.

Unit of Measure: milliseconds (ms)

QRS duration (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Monitored for potential ventricular conduction abnormalities. Clinically significant changes are reported as adverse events.

Unit of Measure: milliseconds (ms)

QT interval (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Used for cardiac repolarization safety assessment.

Unit of Measure: milliseconds (ms)

Corrected QT interval (QTc, milliseconds) is calculated from the QT interval on a standard 12-lead electrocardiogram (recorded after ≥5 minutes rest, supine position, calibrated equipment) using Bazett or Fridericia formula as specified in the protocol. Interpreted by qualified cardiologists or trained investigators. QTc prolongation (e.g., >500 ms) is considered clinically significant and reported as an adverse event. Key cardiac safety parameter.

Unit of Measure: milliseconds (ms)

"Shang Huo" often translated as excess internal heat or fire syndrome in Traditional Chinese Medicine. Key symptoms include: Dry mouth / thirst; Oral ulcers or sores on tongue/mouth; Swollen and painful gums; Increased appetite with easy hunger; Constipation; Other possible accompanying symptoms (e.g., sore throat, red eyes, irritability, if protocol-defined).

Adverse events will be evaluated in terms of type, incidence, severity, time of onset, and relationship to the study drug.

Types of adverse events are classified as: Adverse Event (AE), Serious Adverse Event (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR).

Severity is graded as: mild, moderate, or severe. Mild: The subject can tolerate the event; it does not interfere with ongoing treatment, requires no special intervention, and has no impact on the subject's recovery.

Moderate: The subject finds the event difficult to tolerate; it necessitates discontinuation of the study drug or special treatment, and it directly affects the subject's recovery.

Severe: The event is life-threatening, results in death or permanent disability/incapacity, and requires immediate discontinuation of the study drug or emergency intervention.

Plasma concentration measured from blood samples collected opportunistically at Week 4 (or Week 8/early discontinuation). Cmax is the maximum observed concentration post-dose. Parameters estimated using non-compartmental analysis or population PK modeling due to sparse sampling. Geometric mean and variability reported. Assessed as an exploratory pharmacokinetic biomarker.

Unit of Measure: ng/mL (or appropriate unit, e.g., nmol/L)

Blood samples collected opportunistically at Week 4 and at Week 8 (or early termination), ideally at pre-dose timing where possible. Plasma concentration of [Drug Name] measured using validated bioanalytical methods. Ctrough is the observed minimum concentration at the end of the dosing interval. Reported as geometric mean and variability. Exploratory pharmacokinetic endpoint focusing on steady-state trough exposure.

Unit of Measure: ng/mL (or nmol/L, adjust based on drug)

Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-last) , estimated from sparse opportunistic sampling at Week 4 (or Week 8) using population PK methods. Geometric mean reported. Exploratory PK biomarker of exposure.

Unit of Measure: h·ng/mL (or appropriate, e.g., h·nmol/L

Fecal samples collected at baseline and Week 8 . Multi-omics analysis (including gut microbiome profiling via 16S rRNA sequencing or metagenomics, and fecal metabolomics via targeted/untargeted methods) performed to assess overall changes in microbial composition, diversity, and metabolic products (e.g., short-chain fatty acids and other microbial-derived metabolites). Changes from baseline evaluated as exploratory biomarkers of treatment effects on gut microbiota and related metabolic pathways.

Unit of Measure: Varies by assay (e.g., relative abundance %, μmol/g feces, diversity indices)

Blood samples collected at baseline, Week 4 (opportunistic sampling), and Week 8. Multi-omics analysis (including targeted/untargeted metabolomics and proteomics) performed on plasma to assess systemic changes in metabolites (e.g., tryptophan pathway intermediates) and proteins (e.g., inflammatory markers or neurotrophic factors). Changes from baseline evaluated as exploratory biomarkers of treatment effects on systemic metabolism and inflammation.

Unit of Measure: Varies by assay (e.g., nmol/L or pg/mL)