Bacteriology and Inflammation in Bronchiectasis

NCT ID: NCT01761214

Last Updated: 2020-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2023-12-31

Brief Summary

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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

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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.

Conditions

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Bronchiectasis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Fluroquinolones

Intervention Type DRUG

All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis

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.

Group Type ACTIVE_COMPARATOR

Beta-lactamase inhibitor

Intervention Type DRUG

All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.

Interventions

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Fluroquinolones

All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis

Intervention Type DRUG

Beta-lactamase inhibitor

All antibiotics are administered based on British Thoracic Society guideline for bronchiectasis.

Intervention Type DRUG

Other Intervention Names

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levoflocaxin (Cravit) moxifloxacin (Avelox) ciprofloxacin (Cifran) amoxicillin clavulanate potassium compound (Junerqing)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guangzhou Institute of Respiratory Disease

OTHER

Sponsor Role lead

Responsible Party

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Weijie Guan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nan-shan Zhong, M. D.

Role: PRINCIPAL_INVESTIGATOR

Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College

Rong-chang Chen, M. D.

Role: PRINCIPAL_INVESTIGATOR

Sate Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College

Locations

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

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Facility Contacts

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Nan-shan Zhong, M. D.

Role: primary

020-83062718

Rong-chang Chen, M. D.

Role: backup

020-83062718

References

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Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.

Reference Type BACKGROUND
PMID: 11986413 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18238949 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18829674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15741443 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20627931 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9730996 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10669685 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16936234 (View on PubMed)

Zheng J, Zhong N. Normative values of pulmonary function testing in Chinese adults. Chin Med J (Engl). 2002 Jan;115(1):50-4.

Reference Type BACKGROUND
PMID: 11930658 (View on PubMed)

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.

Reference Type RESULT
PMID: 22744718 (View on PubMed)

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.

Reference Type RESULT
PMID: 19501498 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27339787 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26904207 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26060319 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25654540 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25405614 (View on PubMed)

Other Identifiers

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SKLRD-2013-GWJ

Identifier Type: -

Identifier Source: org_study_id

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