search
Back to results

Bacteriology and Inflammation in Bronchiectasis (BISER)

Primary Purpose

Bronchiectasis

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Fluroquinolones
Beta-lactamase inhibitor
Sponsored by
Guangzhou Institute of Respiratory Disease
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bronchiectasis focused on measuring bacteriology, inflammation, bronchiectasis, exacerbation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Fluroquinolones

Beta-lactamase inhibitor

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Sputum microbiology
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
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
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
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
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
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 to recovery of respective symptom
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
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.

Full Information

First Posted
January 3, 2013
Last Updated
February 8, 2020
Sponsor
Guangzhou Institute of Respiratory Disease
search

1. Study Identification

Unique Protocol Identification Number
NCT01761214
Brief Title
Bacteriology and Inflammation in Bronchiectasis
Acronym
BISER
Official Title
Bacteriology and Sputum and Systemic Inflammation in Steady-state, Acute Exacerbation and Recovery of Bronchiectasis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Recruiting
Study Start Date
September 2012 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Guangzhou Institute of Respiratory Disease

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiectasis
Keywords
bacteriology, inflammation, bronchiectasis, exacerbation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fluroquinolones
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Beta-lactamase inhibitor
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fluroquinolones
Other Intervention Name(s)
levoflocaxin (Cravit), moxifloxacin (Avelox), ciprofloxacin (Cifran)
Intervention Description
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis
Intervention Type
Drug
Intervention Name(s)
Beta-lactamase inhibitor
Other Intervention Name(s)
amoxicillin clavulanate potassium compound (Junerqing)
Intervention Description
All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.
Primary Outcome Measure Information:
Title
Sputum microbiology
Description
type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Sputum sol phase inflammatory indices
Description
sputum sol phase interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), myeloperoxidase (MPO) and C-reactive protein (CRP)
Time Frame
1 year
Title
24-hour sputum volume
Description
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.
Time Frame
1 year
Title
Spirometry
Description
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.
Time Frame
1 year
Title
Sputum purulence
Description
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.
Time Frame
1 year
Title
Sputum viscosity
Description
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.
Time Frame
1 year
Title
SGRQ total score and the score of each domain
Time Frame
1 year
Title
Time to recovery of respective symptom
Description
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.
Time Frame
1 year
Title
Sputum bacterial clearance rate
Description
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nan-shan Zhong, M. D.
Organizational Affiliation
Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rong-chang Chen, M. D.
Organizational Affiliation
Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nan-shan Zhong, M. D.
Phone
020-83062718
Email
nanshan@vip.163.com
First Name & Middle Initial & Last Name & Degree
Rong-chang Chen, M. D.
Phone
020-83062718
Email
chenrc99@hotmail.com
First Name & Middle Initial & Last Name & Degree
Wei-jie Guan, Ph. D.
First Name & Middle Initial & Last Name & Degree
Zhi-ya Lin, Ph. D.
First Name & Middle Initial & Last Name & Degree
Nan-shan Zhong, M. D.
First Name & Middle Initial & Last Name & Degree
Rong-chang Chen, M. D.
First Name & Middle Initial & Last Name & Degree
Yong-hua Gao, Ph. D.
First Name & Middle Initial & Last Name & Degree
Gang Xu, Ph. D.

12. IPD Sharing Statement

Citations:
PubMed Identifier
11986413
Citation
Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.
Results Reference
background
PubMed Identifier
18238949
Citation
Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J. 2008 Feb;31(2):396-406. doi: 10.1183/09031936.00069007.
Results Reference
background
PubMed Identifier
18829674
Citation
Murray MP, Turnbull K, Macquarrie S, Hill AT. Assessing response to treatment of exacerbations of bronchiectasis in adults. Eur Respir J. 2009 Feb;33(2):312-8. doi: 10.1183/09031936.00122508. Epub 2008 Oct 1.
Results Reference
background
PubMed Identifier
15741443
Citation
Tsang KW, Tan KC, Ho PL, Ooi GC, Ho JC, Mak J, Tipoe GL, Ko C, Yan C, Lam WK, Chan-Yeung M. Inhaled fluticasone in bronchiectasis: a 12 month study. Thorax. 2005 Mar;60(3):239-43. doi: 10.1136/thx.2002.003236.
Results Reference
background
PubMed Identifier
20627931
Citation
Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.
Results Reference
background
PubMed Identifier
9730996
Citation
Tsang KW, Ho PL, Lam WK, Ip MS, Chan KN, Ho CS, Ooi CC, Yuen KY. Inhaled fluticasone reduces sputum inflammatory indices in severe bronchiectasis. Am J Respir Crit Care Med. 1998 Sep;158(3):723-7. doi: 10.1164/ajrccm.158.3.9710090.
Results Reference
background
PubMed Identifier
10669685
Citation
Tsang KW, Chan K, Ho P, Zheng L, Ooi GC, Ho JC, Lam W. Sputum elastase in steady-state bronchiectasis. Chest. 2000 Feb;117(2):420-6. doi: 10.1378/chest.117.2.420.
Results Reference
background
PubMed Identifier
16936234
Citation
Laszlo G. Standardisation of lung function testing: helpful guidance from the ATS/ERS Task Force. Thorax. 2006 Sep;61(9):744-6. doi: 10.1136/thx.2006.061648.
Results Reference
background
PubMed Identifier
11930658
Citation
Zheng J, Zhong N. Normative values of pulmonary function testing in Chinese adults. Chin Med J (Engl). 2002 Jan;115(1):50-4.
Results Reference
background
PubMed Identifier
22744718
Citation
Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012 Oct 1;186(7):657-65. doi: 10.1164/rccm.201203-0487OC. Epub 2012 Jun 28.
Results Reference
result
PubMed Identifier
19501498
Citation
Kapur N, Masters IB, Chang AB. Exacerbations in noncystic fibrosis bronchiectasis: Clinical features and investigations. Respir Med. 2009 Nov;103(11):1681-7. doi: 10.1016/j.rmed.2009.05.007. Epub 2009 Jun 6.
Results Reference
result
PubMed Identifier
27339787
Citation
Guan WJ, Yuan JJ, Gao YH, Li HM, Zheng JP, Chen RC, Zhong NS. Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis. Sci Rep. 2016 Jun 24;6:28467. doi: 10.1038/srep28467.
Results Reference
derived
PubMed Identifier
26904207
Citation
Guan WJ, Gao YH, Xu G, Li HM, Yuan JJ, Zheng JP, Chen RC, Zhong NS. Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications. J Thorac Dis. 2016 Jan;8(1):14-23. doi: 10.3978/j.issn.2072-1439.2016.01.05.
Results Reference
derived
PubMed Identifier
26060319
Citation
Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Jiang M, Zheng JP, Chen RC, Zhong NS. Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations. Respir Care. 2015 Aug;60(8):1180-9. doi: 10.4187/respcare.04004. Epub 2015 Jun 9.
Results Reference
derived
PubMed Identifier
25654540
Citation
Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Impulse oscillometry in adults with bronchiectasis. Ann Am Thorac Soc. 2015 May;12(5):657-65. doi: 10.1513/AnnalsATS.201406-280OC.
Results Reference
derived
PubMed Identifier
25405614
Citation
Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Characterization of lung function impairment in adults with bronchiectasis. PLoS One. 2014 Nov 18;9(11):e113373. doi: 10.1371/journal.pone.0113373. eCollection 2014.
Results Reference
derived

Learn more about this trial

Bacteriology and Inflammation in Bronchiectasis

We'll reach out to this number within 24 hrs