Adjunctive Therapy of Andrographolid Sulfonatein Community Acquired Pneumonia

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 462
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chen Wang, Professor; Phone Number: +86 13901122992; Email: cyh-birm@263.net
• Study Contact Backup: Name: Bin Cao, Professor; Phone Number: +86 13911318339; Email: caobin_ben@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: Xiaojing Cui, MD; Phone Number: +86 10 84206269; Email: cuixiaojing86@163.com
      • Contact: Bin Cao, MD; Phone Number: +86 13911318339; Email: caobin_ben@163.com
    • Beijing, Beijing, China
      • Active, not recruiting
      • Beijing ChaoYang Hospital
    • Beijing, Beijing, China
      • Active, not recruiting
      • Beijing Hospital of TCM
    • Beijing, Beijing, China
      • Active, not recruiting
      • Beijing Luhe Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Recruiting
      • Fu Xing Hospital, Capital Medical Unviersity
      • Contact: Jin Chen, MD
  • Fujian
    • Wenzhou, Fujian, China
      • Active, not recruiting
      • The First Affiliated Hospital of Wenzhou University
  • Hebei
    • QinHuangDao, Hebei, China
      • Active, not recruiting
      • First Hospital of Qinhuangdao
    • Shijiazhuang, Hebei, China
      • Active, not recruiting
      • The second hospital of Hebei Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Active, not recruiting
      • Nanjing General Hospital
  • Jiangxi
    • NanChang, Jiangxi, China
      • Active, not recruiting
      • The First Affiliated Hospital of Nanchang University
  • Liaoning
    • Shenyang, Liaoning, China
      • Active, not recruiting
      • The First Hospital of China Medical University
  • Shandong
    • Qingdao, Shandong, China
      • Active, not recruiting
      • Qingdao Municipal Hospital
    • ZiBo, Shandong, China
      • Active, not recruiting
      • The Central Hospital of ZiBo City
  • Shanxi
    • Taiyuan, Shanxi, China
      • Active, not recruiting
      • The First Hospital of Shanxi Medical University
  • Sichuan
    • Chengdu, Sichuan, China
      • Active, not recruiting
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Active, not recruiting
      • The General Hospital of Tianjin Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Qingfeng Pharmaceutical Group
• Investigators: Principal Investigator: Chen Wang, Professor, China-Japan Friendship Hospital; Principal Investigator: Bin Cao, Professor, China-Japan Friendship Hospital; Principal Investigator: Jin Chen, Professor, Fu Xing Hospital, Capital Medical University; Principal Investigator: Yuguang Wang, Professor, Beijing Hospital of TCM; Principal Investigator: Li Gu, Professor, Beijing Chao Yang Hospital; Principal Investigator: Zhenyang Xu, Professor, Beijing Luhe Hospital, Capital Medical University; Principal Investigator: Yan Yi, Professor, First Hospital of China Medical University; Principal Investigator: Wei Zhang, Professor, The First Affiliated Hospital of Nanchang University; Principal Investigator: Shufeng Xu, Professor, First Hospital of Qinhuangdao; Principal Investigator: Bo Liu, Professor, The Central Hospital of ZiBo City; Principal Investigator: Jie Cao, Professor, The General Hospital of Tianjin Medical University; Principal Investigator: Yuping Li, Professor, The First Affiliated Hospital of Wenzhou University; Principal Investigator: Xuedong Liu, Professor, Qingdao Municipal Hospital; Principal Investigator: Hong Fan, Professor, West China Hospital; Principal Investigator: Zhigang Cai, Professor, The second hospital of Hebei Medical University; Principal Investigator: Xinri Zhang, Professor, The First Affiliated Hospital of Shanxi Medical University; Principal Investigator: Xin Su, Professor, Nanjing General Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): June 30, 2019

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: September 21, 2016
• First Posted (Estimate): September 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Amoxicillin; Azithromycin; Fluoroquinolones; Minocycline; Cephalosporins
• Other Study ID Numbers: QF-CAP-20160402