Adjunctive Therapy of Andrographolid Sulfonatein Community Acquired Pneumonia

Phase 4

• Conditions: Community Acquired Pneumonia
• Interventions: Drug: Andrographolid Sulfonate Injection (AS Injection); Drug: Azithromycin, Minocycline or Doxycycline; Drug: Cephalosporin; Drug: Amoxicillin-clavulantic acid; Drug: Fluoroquinolones; Drug: Placebo

• Registration Number: NCT02913118
• Lead Sponsor: Qingfeng Pharmaceutical Group

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-09-12
• Study First Submitted QC: 2016-09-21
• Study First Posted: 2016-09-23
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-09
• Last Update Posted: 2018-04-10
• Primary Completion: 2019-01
• Study Completion: 2019-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 462

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)

  1. Pneumonia that is acquired in community
  2. Symptoms and signs of pneumonia:
  <!-- -->
  1. Presence of cough, expectoration or exacerbation of chronic airways disease, with or without purulent sputum/chest pain/dyspnea/hemoptysis.
  2. Presence offever.
  3. Lung consolidation and/or moist rales.
  4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
standard antibiotic treatment + AS placebo	Azithromycin, Minocycline or Doxycycline	AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment + AS placebo	Amoxicillin-clavulantic acid	AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment +AS injection	Amoxicillin-clavulantic acid	Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment +AS injection	Andrographolid Sulfonate Injection (AS Injection)	Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment +AS injection	Cephalosporin	Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment +AS injection	Azithromycin, Minocycline or Doxycycline	Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment + AS placebo	Cephalosporin	AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment + AS placebo	Fluoroquinolones	AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment +AS injection	Fluoroquinolones	Andrographolid Sulfonate Injection (AS Injection) plus one of 3 antibiotics in China CAP Guideline
standard antibiotic treatment + AS placebo	Placebo	AS placebo (NS injection) plus one of 3 antibiotics in China CAP Guideline

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
the duration of fever	14 days
length of stay in hospital	14 days
questionnaire for hospitalization expenses	14 days
the rate of diarrhea and intestinal dysbacteriosis	14 days
the duration of intravenous antibiotic treatment	14 days
the initial treatment failure rate	14 days

Trial Locations

Locations (16)

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Chaoyang Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Hospital of TCM; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Wenzhou University; 🇨🇳 Wenzhou, Fujian, China

First Hospital of QinHuangDao; 🇨🇳 QinHuangDao, Hebei, China

The Second Hospital of Hebei Medical University; 🇨🇳 Shijiazhuang, Hebei, China

Beijing LuHe Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Fu Xing Hospital, Capital Medical Unviersity; 🇨🇳 Beijing, Beijing, China

Nanjing General Hospital; 🇨🇳 Nanjing, Jiangsu, China

The First Affiliated Hospital of NanChang University; 🇨🇳 NanChang, Jiangxi, China

Qingdao Municipal Hospital; 🇨🇳 Qingdao, Shandong, China

The First Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

The Central Hospital of ZiBo City; 🇨🇳 ZiBo, Shandong, China

The First Hospital of Shanxi Medical University; 🇨🇳 Taiyuan, Shanxi, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

The General Hospital of Tianjin Medical University; 🇨🇳 Tianjin, Tianjin, China