Adjunctive Therapy of Andrographolid Sulfonatein Community Acquired Pneumonia

Study Overview
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Brief Summary
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Adjunctive Therapy of AndrographolidSulfonate in Community Acquired Pneumonia: A Multicenter, Randomized,Double-blinded, Placebo Controlled Clinical Trial. The hypothesis is that combination therapy with Andrographolid Sulfonatein injection and antibacterial is significantly better than antibacterial alone in achieving clinical stability among hospitalized CAP patients.

Official Title
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Adjunctive Therapy of Andrographolid Sulfonatein Community Acquired Pneumonia: A Multicenter Randomized Controlled Clinical Trial

Conditions
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Community Acquired Pneumonia

Intervention / Treatment
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* Drug: Andrographolid Sulfonate Injection (AS Injection)
* Drug: Cephalosporin
* Drug: Azithromycin, Minocycline or Doxycycline
* Drug: Amoxicillin-clavulantic acid
* Drug: Fluoroquinolones
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18-75 years, no gender restrictions. Voluntary participation, all participants provide written informed consent. Volunteers are hospitalized patients Patients are hospitalized for community acquired pneumonia with T≥38°C within 24 hours before being enrolled Diagnosis of CAP(Chinese Guideline for Diagnosis and Management of Community Acquired Pneumonia in Adults 2016) Pneumonia that is acquired in community Symptoms and signs of pneumonia: Presence of cough, expectoration or exacerbation of chronic airways disease, with or without purulent sputum/chest pain/dyspnea/hemoptysis. Presence offever. Lung consolidation and/or moist rales. Peripheral blood（WBC）>10×109/L or <4×109/L, with or without nuclear left shift; 3. Chest radiograph shows new ground-glass opacity, patchy infiltration, consolidation or interstitial changes, with or without pleural effusion. Patients who meet 1,3 and any one item in 2, exclude one of the following are clinically classified as CAP: pulmonary tuberculosis, cancer, non-infectious interstitial lung disease, pulmonary edema, atelectasis, pulmonary embolism, pulmonary eosinophilia and pulmonary vasculitis. CURB 65≥1 point,Each risk factor scores one point, for a maximum score of 5: Confusion of new onset Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL) Respiratory rate of 30 breaths per minute or greater Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less Age 65 or older Within 72 hours after symptom onset Exclusion Criteria: Known allergy to AS Pregnant or breast-feeding Heart dysfunction, NYHA III-IV class Hematological system diseases, such as lymphoma, leukemia, agranulocytosis (neutrophil count< 0.5×109/L). Autoimmune diseases and disease active Terminal malignant tumor Long-term treatment of high dose corticosteroids (prednisone 10mg/d ≥2 weeks) or immunosuppressive agents Inflammatory bowel disease, such as Crohn's disease, ulcerative colitis Chronic renal failure, eGFR<50 ml/min/1.73m2 Severe liver function damage, ALT or AST greater than or equal to 2 times the upper limit of normal Hypernatremia, serum sodium≥145mmol/L Diagnosis as severe pneumonia: Diagnostic criteria of severe pneumonia: patients who meet one major criteria or at least 3 of these minor criteria are classified as severe cases: Major criteria:①the need for invasive mechanical ventilation②sepsis shock after active fluid resuscitation still need vasoactive drugs; Minor criteria:①respiratory rate >30 breaths/min, ②PaO2/FiO2≤250mmHg（1mmHg=0.133kPa）, ③multilobar infiltrates, ④confusion or/andunorientation, ⑤bloodurea nitrogen level≥20mg/dl（7.14mmol/L）, ⑥systolic pressure <90mmHg need active fluid resuscitation Defervescence by using corticosteroid after symptom onset. Patients who participated another intervention study within a month Other conditions not suitable for inclusion according to the investigator' judgment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard antibiotic treatment +AS injection<br>Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline | Drug: Andrographolid Sulfonate Injection (AS Injection)<br> <br> Drug: Cephalosporin<br> <br> Drug: Azithromycin, Minocycline or Doxycycline<br> <br> Drug: Amoxicillin-clavulantic acid<br> <br> Drug: Fluoroquinolones<br> <br> |
| Placebo Comparator: standard antibiotic treatment + AS placebo<br>AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline | Drug: Cephalosporin<br> <br> Drug: Azithromycin, Minocycline or Doxycycline<br> <br> Drug: Amoxicillin-clavulantic acid<br> <br> Drug: Fluoroquinolones<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to clinical stability |  | 14 days | 
| number of study participants with treatment-related adverse events as assessed by CTCAE v4.0 | symptoms and signs, blood and urine routine, liver and kidney function monitoring, ECG, side effects of long-time using of antibiotics | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the duration of fever |  | 14 days | 
| the initial treatment failure rate |  | 14 days | 
| length of stay in hospital |  | 14 days | 
| questionnaire for hospitalization expenses |  | 14 days | 
| the duration of intravenous antibiotic treatment |  | 14 days | 
| the rate of diarrhea and intestinal dysbacteriosis |  | 14 days |