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Infectious Pathogens in Acute Respiratory Illness in Adults and Elderly

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ClinicalTrials.gov Identifier: NCT01360398
Recruitment Status : Completed
First Posted : May 25, 2011
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The aim of this study is to generate epidemiological data to further explore determinants of Chronic Obstructive Pulmonary Disease (COPD) and the contribution of bacterial and viral pathogens to Acute Exacerbation of COPD (AECOPD) episodes.

Condition or disease Intervention/treatment Phase
Respiratory Disorders Procedure: Blood sample Procedure: Sputum sample Procedure: Nasopharyngeal swab Procedure: Urine sample Procedure: End tidal breath sample Other: Data collection Other: Tests Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Contribution of Infectious Pathogens to Acute Respiratory Illness in Adults and Elderly
Actual Study Start Date : June 30, 2011
Actual Primary Completion Date : June 27, 2014
Actual Study Completion Date : June 27, 2014

Arm Intervention/treatment
Cohort
COPD male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices.
Procedure: Blood sample
Blood samples will be collected from all patients at enrolment, at follow-up visits, at exacerbation visits, and during the final visit.

Procedure: Sputum sample
Sputum will be collected from all patients at enrolment, at monthly follow-up visits, at exacerbation visits, and during the final visit. Sputum will be obtained by spontaneous expectoration or induced by stimulation according to standard methods.

Procedure: Nasopharyngeal swab
Nasopharyngeal swabs will be collected from all patients at enrolment and from a subcohort of 30 patients at monthly follow-up visits and at exacerbation visits during the first year.

Procedure: Urine sample
Urine samples will be taken at enrolment and exacerbation visits from all subjects and from the same subcohort of 30 patients providing nasopharyngeal swabs, at monthly follow-up visits during the first year.

Procedure: End tidal breath sample
Breath samples will be collected from all patients at enrolment, at follow-up visits (monthly), at exacerbation visits, and during the final visit.

Other: Data collection
Patient interview, diary cards review and questionnaires completion

Other: Tests
Urine pregnancy test, chest CT-scan, lung function testing and 6-min walk test




Primary Outcome Measures :
  1. Mean Estimated Number of Acute Exacerbation of COPD (AECOPD) [ Time Frame: During year 1 ]
    An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD The Means and Confidence Intervals (CI) were estimated using the Negative Binomial model taking into account time to follow up. Estimated exacerbations were presented as mean number of exacerbations per (/) subject/ year.

  2. Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens [ Time Frame: During Year 1 ]
    Bacterial pathogens assessed were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Steptococcus pneumoniae (Sp), Staphylococcus Aureus (Sta), Pseudomonas aeruginosa (Psa), any or other. For each bacteria, the means and CIs were estimated from Negative Binomial model taking into account the follow up time.Estimated exacerbations were presented as mean number of exacerbations/ subject/ year.

  3. Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum [ Time Frame: During Year 1 ]
    Bacterial pathogens assessed, by culture, were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Streptococcus pneumoniae (Sp), Staphylococcus aureus (Sta), Pseudomonas aeruginosa (Psa), any bacteria or other bacteria. Overall exacerbation rate is the average number of exacerbations for each subject during their time in the study.


Secondary Outcome Measures :
  1. Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi [ Time Frame: During Year 1 ]
    Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for any bacteria and Hi.

  2. Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp [ Time Frame: During Year 1 ]
    Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Mcat and Sp.

  3. Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria [ Time Frame: During Year 1 ]
    Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Sta, Psa and other bacteria.

  4. Mean Number of Days Between 2 Consecutive AECOPDs [ Time Frame: During Year 1 ]
    The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.

  5. Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit [ Time Frame: During Year 1 ]
    The exacerbations of chronic pulmonary disease tool version 1.0 (EXACT) is a validated self-administered instrument that evaluates the effects of pharmacologic treatment on acute exacerbations of COPD. Analyses of exacerbations in relation to morning or evening EXACT-PRO e-diaries were presented as follows: descriptive statistics on the EXACT daily scores tabulated at enrolment, at any stable and at any, mild, moderate or severe exacerbation visit. EXACT-PRO contains 14 questions with scores ranging from 0 to 4, where 0= best outcome while 4= worse outcome.

  6. Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit [ Time Frame: During Year 1 ]
    The COPD assessment test (CAT) is a validated self-administered instrument designed to provide a simple and reliable measure of health status in COPD patients. Its properties have been shown to be similar to the St George's respiratory questionnaire (SGRQ). The CAT comprises 8 items and has a scoring range of 0-40, 0= most positive answer and 40= most negative answer. In this study, the subjects were to complete the CAT questionnaire every 3 months.

  7. Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit [ Time Frame: During Year 1 ]
    The NEADL assessed (quarterly in the present study) the ease or difficulty in performing extended activities of daily living. The NEADL scale contains 22 items, each measured on a 4-point Likert scale. There are four dimensions: mobility (6 items); kitchen (5 items); domestic (5 items); leisure (6 items). These are summed producing a total score reflecting general functioning. Each of the 22 individual items had 2 possible scores (0 or 1). Therefore, the range of the NEADL score was 0 to 22. Lower scores indicate greater levels of disability while higher scores indicate greater independence.

  8. Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit [ Time Frame: During Year 1 ]
    The EQ-5D is an established measure of generic health outcome that provides a simple descriptive profile and a single index value that can be used in clinical and economic evaluation of healthcare and in population surveys. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 100 (best health state). The negative numbers presented represent a decrease from baseline values and a worsening of health.

  9. Number of Subjects Receiving Various Health Care Types During AECOPD [ Time Frame: During Year 1 ]
    AECOPD health care type included: general practitioners (other than the study doctor), pneumologists, other specialists, hospital emergency department, home care nurses, pulmonary rehabilitation programs and/or nutrition advices.

  10. Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal [ Time Frame: During Year 1 ]
    Serious adverse events (SAEs) include medical occur-rences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disabil-ity/incapacity.

  11. AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay [ Time Frame: During Year 1 ]
    Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.

  12. AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [ Time Frame: During Year 1 ]
    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus.

  13. Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [ Time Frame: During Year 1 ]
    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Mild exacerbations were defined as worsening symptoms of COPD that were self-managed by the patient.

  14. Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [ Time Frame: During Year 1 ]
    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Moderate exacerbations were defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics.

  15. Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [ Time Frame: During Year 1 ]
    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Severe exacerbations were defined as worsening symptoms of COPD that required treatment with in-patient hospitalisation or home care intervention.

  16. AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity [ Time Frame: During Year 1 ]
    An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD. AECOPD severity was assessed as: any, mild, moderate and severe. Any = any COPD symptom regardless of severity. Mild = Worsening symptoms of COPD that are self-managed by the patient. Moderate = Worsening symptoms of COPD that require treatment with oral corticosteroids and/or antibiotics. Severe = Worsening symptoms of COPD that require treatment with in-patient hospitalisation or home care intervention.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol.
  • Written informed consent obtained from the subject.
  • Male or female subjects between, and including, 40 and 85 years of age, at the time of consent.
  • Subjects with confirmed diagnosis of COPD with Forced Expiratory Volume of air expired in 1 second (FEV1) of </=80% of predicted normal and FEV1/Forced expiratory Vital Capacity (FVC)<0.7
  • Subjects have moderate, severe, or very severe COPD, according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging.
  • Subjects have a current or prior history of >/=10 pack-years of cigarette smoking. Former smokers are defined as those who have stopped smoking for at least 6 months. Number of pack years = (number of cigarettes per day/20) x number of years smoked.
  • Subjects present a documented history of >/=1 exacerbation requiring antibiotics and/or oral corticosteroids or hospitalization in the previous 12 months.

Exclusion Criteria:

  • Subject also has a confirmed diagnosis of asthma, cystic fibrosis, pneumonia risk factors or other respiratory disorders.
  • Subjects having undergone lung surgery.
  • Subject has a α-1 antitrypsin deficiency as underlying cause of COPD.
  • Subject who experienced a moderate or severe COPD exacerbation not resolved at least 1 month prior to enrolment visit and at least 30 days following the last dose of oral corticosteroids.
  • Subject using any antibacterial, antiviral or respiratory investigational drug or relevant vaccine up to 30 days prior to the enrolment visit.
  • Subject has other conditions that the principal investigator judges may interfere with the study findings. Women who are pregnant or lactating or are planning on becoming pregnant during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01360398


Locations
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United Kingdom
GSK Investigational Site
Southampton, Hampshire, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 114378
For additional information about this study please refer to the GSK Clinical Study Register

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01360398    
Other Study ID Numbers: 114378
First Posted: May 25, 2011    Key Record Dates
Results First Posted: February 15, 2019
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Keywords provided by GlaxoSmithKline:
pathogen
Chronic Obstructive Pulmonary Disease
Acute Exacerbations of Chronic Obstructive Pulmonary Disease
COPD
respiratory
AECOPD
exacerbation
Additional relevant MeSH terms:
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Respiration Disorders
Respiratory Tract Diseases