Infectious Pathogens in Acute Respiratory Illness in Adults and Elderly

Respiratory Disorders Clinical Trial

Official title:

Contribution of Infectious Pathogens to Acute Respiratory Illness in Adults and Elderly

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01360398
• Other study ID #: 114378
• Status: Completed
• Phase: N/A
• Start date: June 30, 2011
• Est. completion date: June 27, 2014

Study information

• Verified date: February 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: June 27, 2014
• Est. primary completion date: June 27, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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 a-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.

Related Conditions & MeSH terms

• Respiration Disorders
• Respiratory Disorders
• Respiratory Tract Diseases

Intervention

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

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Southampton	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Bourne S, Cohet C, Kim V, Barton A, Tuck A, Aris E, Mesia-Vela S, Devaster JM, Ballou WR, Clarke SC, Wilkinson T. Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study. BMJ Open. 2014 Mar 7;4(3):e004546. doi: 10.1136/bmjopen-2013-004546. Erratum in: BMJ Open. 2015;5(1):e004546corr1. Clarke, Stuart [corrected to Clarke, Stuart C]. — View Citation

Mayhew D, Devos N, Lambert C, Brown JR, Clarke SC, Kim VL, Magid-Slav M, Miller BE, Ostridge KK, Patel R, Sathe G, Simola DF, Staples KJ, Sung R, Tal-Singer R, Tuck AC, Van Horn S, Weynants V, Williams NP, Devaster JM, Wilkinson TMA; AERIS Study Group. Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations. Thorax. 2018 May;73(5):422-430. doi: 10.1136/thoraxjnl-2017-210408. Epub 2018 Jan 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Estimated Number of Acute Exacerbation of COPD (AECOPD)	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.	During year 1
Primary	Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens	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.	During Year 1
Primary	Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum	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.	During Year 1
Secondary	Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi	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.	During Year 1
Secondary	Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp	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.	During Year 1
Secondary	Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria	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.	During Year 1
Secondary	Mean Number of Days Between 2 Consecutive AECOPDs	The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.	During Year 1
Secondary	Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Secondary	Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Secondary	Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Secondary	Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Secondary	Number of Subjects Receiving Various Health Care Types During AECOPD	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.	During Year 1
Secondary	Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal	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.	During Year 1
Secondary	AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay	Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.	During Year 1
Secondary	AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Secondary	Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Secondary	Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Secondary	Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Secondary	AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity	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.	During Year 1

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