Bacteriology and Inflammation in Bronchiectasis (BISER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Guangzhou Institute of Respiratory Disease
Sponsor:
Information provided by (Responsible Party):
Weijie Guan, Guangzhou Institute of Respiratory Disease
ClinicalTrials.gov Identifier:
NCT01761214
First received: January 3, 2013
Last updated: NA
Last verified: January 2013
History: No changes posted
  Purpose

Bronchiectasis is a chronic disease arises from progressive airway inflammation and infection. It has been postulated that bacterial infection triggers intense airway inflammation leading to acute exacerbation of bronchiectasis. Antibiotics have been the most potent medications for the treatment of bronchiectasis, however, the sputum bacterial load and inflammatory indices at steady-state and exacerbation remain largely unknown. The investigation might shed light on the roles that antibiotics play in acute exacerbation of bronchiectasis and uncover the mechanisms on why a subgroup of individuals do not respond satisfactorily.


Condition Intervention
Bronchiectasis
Drug: Fluroquinolones
Drug: Beta-lactamase inhibitor

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bacteriology and Sputum and Systemic Inflammation in Steady-state, Acute Exacerbation and Recovery of Bronchiectasis

Resource links provided by NLM:


Further study details as provided by Guangzhou Institute of Respiratory Disease:

Primary Outcome Measures:
  • Sputum microbiology [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter


Secondary Outcome Measures:
  • Sputum sol phase inflammatory indices [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    sputum sol phase interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), myeloperoxidase (MPO) and C-reactive protein (CRP)

  • 24-hour sputum volume [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    Eligible patients with bronchiectasis, following recruitment, will be instructed to record the condition of expectoration in the patient diary card. This includes recording of 24-hour sputum volume, sputum purulence and changes in the symptoms per day. A minimum of 3 daily records between two neighboring visits are required. The 24-hour sputum volume will be recorded as the mean of 3 records.

    The volume of 24-hour sputum was recorded as the mean of the nearest 3 consecutive days. Sputum volume was scored for 1, 2, 3, 4, 5 and 6 points corresponding to 0-10ml, 10-20ml, 20-30ml, 30-40ml, 40-50ml and >50ml, respectively.


  • Spirometry [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    Spirometric indices in the present study is referred to as FEV1, FVC, FEV1/FVC and MMEF.

    Spirometry tests are carried out using a spirometer (COSMED, QUARK PFT, Italy). All operation procedures meet the joint recommendation by ATS and ERS. A total of at least 3 (not more than 8) spirometric maneuvers are performed, with the variation between the best two maneuvers of <5% or 200ml in FVC and FEV1. The maximal values of FVC and FEV1 are reported. MMEF is chosen from the maneuver with the highest sum of FVC and FEV1. The predicted values are selected based on the reference regression model established by Zheng JP and Zhong NS.


  • Sputum purulence [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    Patients receive chest physical therapy 15 minutes upon arrival at the hospital till expectoration complete. Patients are instructed to be seated and remove contents in the oral cavity followed by sputum collection using a sterile container between 10:00 a.m. and 12:00 a.m., an hour after physical therapy.

    Sputum purulence is scored for 1, 2, 3, 4, 5, 6 and 7 points corresponding to complete absence, almost translucent, half translucent, translucent but colorless, opaque and white, grey and green, moderately green and dark green, respectively. The specimen with highest score is selected for reports.


  • Sputum viscosity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Sputum viscosity is assessed by using a stick to randomly pick up the sputum from the center of the specimen. Sputum viscosity is scored for 1, 2 and 3 corresponding to mildly, moderately and severely sticky, respectively.

  • SGRQ total score and the score of each domain [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to recovery of respective symptom [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The symptoms of bronchiectasis include cough, expectoration (referred to as 24-hour sputum volume, purulence and viscosity), chest pain, chest distress, wheezing, febrile, malaise, fatigue, tachypnea and hemoptysis. A significant amelioration (>20%) in the respective symptom during antibiotic treatment when compared with that of acute exacerbation is deemed as recovery. The time of recovery is mainly determined by patient self-reporting.

  • Sputum bacterial clearance rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Sputum bacterial clearance rate is defined as the proportion of subjects who test negatively to sputum microbiology following a 14-day antibiotic therapy, with exception of those who showed a negative sputum culture profile during the steady-state bronchiectasis.


Estimated Enrollment: 80
Study Start Date: September 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fluroquinolones
The fluroquinolones employed in the present study are referred to as oral levofloxacin (500mg q.d.), moxifloxacin (400mg, q.d.) and ciprofloxacin (500mg, b.i.d.). All medications are administered based on the bronchiectasis guideline issued by British Thoracic Society.
Drug: Fluroquinolones
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis
Other Names:
  • levoflocaxin (Cravit)
  • moxifloxacin (Avelox)
  • ciprofloxacin (Cifran)
Active Comparator: Beta-lactamase inhibitor
In the present study, amoxicillin and amoxicillin clavulanate potassium compound are employed, based on the British Thoracic Society guideline for bronchietasis, as mainly determined by sputum microbiology during steady-state bronchiectasis.
Drug: Beta-lactamase inhibitor
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.
Other Name: amoxicillin clavulanate potassium compound (Junerqing)

Detailed Description:

Bronchiectasis is a chronic disease arises from progressive airway inflammation and infection. Pro-inflammatory mediators, the products of activated neutrophils recruited to the inflamed sites, are released in bronchiectatic airways and mediate cascades of neutrophil infiltration. This suggests that bacterial infection plays a pivotal role in the neutrophil-derived inflammation leading to the vicious cycle that perpetuates the development of airway destruction and might result in acute exacerbation. Treatments targeting at bacterial infection is therefore necessary, particularly for those with acute exacerbation of bronchiectasis.

Although short- and long-term administration of antibiotics have been evidenced to markedly suppress bacterial colonization and inflammatory indices, the roles that potent antibiotics play in patients with exacerbation of bronchiectasis are unclear. The assessment of bacterial infection and sputum and systemic inflammation during steady-state, acute exacerbation and recovery from exacerbation of bronchiectasis may clinically shed light on and indicate the efficacy of antibiotic treatments.

Furthermore, a subgroup of patients may experience the acute exacerbation that may stem from non-bacterial pathogens. There has been a dire need to compare the changes in sputum bacterial load and inflammatory indices based on sputum bacteriology. This may help uncover the mechanism of different responses to antibiotic treatment in patients who had varying bacteriologic profiles.

Unlike assessment of chronic obstructive pulmonary disease, few clinical indices for appraisal of onset of exacerbation and efficacy of treatments are available. Of these, the 24-hour sputum volume, microbial clearance, C-reactive protein (CRP) and St George's Respiratory Questionnaire have been validated. In the present study, we employed sputum bacteriology and inflammatory indices, including the aforementioned parameters, for assessment.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of either sex and age between 18 and 70 years

Exclusion Criteria:

  • Patient judged to have poor compliance
  • Female patient who is lactating or pregnant
  • Patients having concomitant severe systemic illnesses (i.e. coronary heart disease, cerebral stroke, uncontrolled hypertension, active gastric ulcer, malignant tumor, hepatic dysfunction, renal dysfunction)
  • Miscellaneous conditions that would potentially influence efficacy assessment, as judged by the investigators
  • Participation in another clinical trial within the preceding 3 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761214

Locations
China, Guangdong
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College Recruiting
Guangzhou, Guangdong, China, 510120
Contact: Nan-shan Zhong, M. D.    020-83062718    nanshan@vip.163.com   
Contact: Rong-chang Chen, M. D.    020-83062718    chenrc99@hotmail.com   
Sub-Investigator: Wei-jie Guan, Ph. D.         
Sub-Investigator: Zhi-ya Lin, Ph. D.         
Principal Investigator: Nan-shan Zhong, M. D.         
Principal Investigator: Rong-chang Chen, M. D.         
Sub-Investigator: Yong-hua Gao, Ph. D.         
Sub-Investigator: Gang Xu, Ph. D.         
Sponsors and Collaborators
Guangzhou Institute of Respiratory Disease
Investigators
Principal Investigator: Nan-shan Zhong, M. D. Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College
Principal Investigator: Rong-chang Chen, M. D. Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College
  More Information

Publications:

Responsible Party: Weijie Guan, Professor, Guangzhou Institute of Respiratory Disease
ClinicalTrials.gov Identifier: NCT01761214     History of Changes
Other Study ID Numbers: SKLRD-2013-GWJ
Study First Received: January 3, 2013
Last Updated: January 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Guangzhou Institute of Respiratory Disease:
bacteriology, inflammation, bronchiectasis, exacerbation

Additional relevant MeSH terms:
Bronchiectasis
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Pathologic Processes
Amoxicillin
Ciprofloxacin
Amoxicillin-Potassium Clavulanate Combination
Clavulanic Acid
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014