Occurrence of Potential Bacterial and Viral Pathogens in Stable Chronic Obstructive Pulmonary Disease and During Acute Exacerbations of the Disease, in Asia Pacific

• ClinicalTrials.gov Identifier: NCT03151395
• Recruitment Status: Completed
• First Posted: May 12, 2017
• Last Update Posted: April 27, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

Since the infectious aetiology of AECOPD has been suggested to vary according to geographical region, the primary purpose of this study (which will be conducted in several countries in Asia Pacific) is to evaluate the occurrence of bacterial and viral pathogens in the sputum of stable COPD patients and at the time of AECOPD. Given the increasing and projected burden of COPD in the Asia Pacific region, this study will also evaluate the frequency, severity and duration of AECOPD, as well as the impact of AECOPD on health-related quality of life (HRQOL), healthcare utilisation and lung function.

Condition or disease	Intervention/treatment	Phase
Respiratory Disorders	Other: Sputum and blood sampling	Not Applicable

Detailed Description:

The protocol has been amended to implement the following changes:

• Alignment of the protocol to the updated GOLD consensus report of 2017 and the COPD fact sheet.
• Alignment of the study endpoints to the study objectives.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 197 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Occurrence of Potential Bacterial and Viral Pathogens in Stable Chronic Obstructive Pulmonary Disease (COPD) and During Acute Exacerbations of COPD (AECOPD), in Asia Pacific
• Actual Study Start Date: August 25, 2017
• Actual Primary Completion Date: April 6, 2020
• Actual Study Completion Date: April 6, 2020

Arms and Interventions

Arm	Intervention/treatment
Total Group; A cohort of approximately 200 moderate to very severe COPD patients with at least 1 documented moderate or severe AECOPD in the year before enrolment and for whom sputum and blood samples will be collected during specified visits.	Other: Sputum and blood sampling; Evaluation of the occurrence of potential bacterial and viral pathogens in the sputum of stable COPD patients and at the time of AECOPD.

Outcome Measures

Primary Outcome Measures :

1. Occurrence of potential bacterial in sputum of stable COPD patients. [ Time Frame: Over the course of 1 year ]
   Bacterial pathogens, as identified by bacteriological methods, including (but not necessarily limited to) Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.
2. Occurrence of potential bacterial in sputum during AECOPD. [ Time Frame: Over the course of 1 year ]
   Bacterial pathogens, as identified by bacteriological methods, including (but not necessarily limited to) Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.
3. Occurrence of viral pathogens in sputum of stable COPD patients. [ Time Frame: Over the course of 1 year ]
   Viral pathogens, as identified by PCR, including (but not necessarily limited to) Respiratory syncytial virus (RSV), parainfluenza virus, enterovirus/ rhinovirus, metapneumovirus, influenza virus, adenovirus, bocavirus and coronavirus and by rhinovirus quantitative RT-PCR.
4. Occurrence of viral pathogens in sputum during AECOPD. [ Time Frame: Over the course of 1 year ]
   Viral pathogens, as identified by PCR, including (but not necessarily limited to) Respiratory syncytial virus (RSV), parainfluenza virus, enterovirus/ rhinovirus, metapneumovirus, influenza virus, adenovirus, bocavirus and coronavirus and by rhinovirus quantitative RT-PCR.

Secondary Outcome Measures :

1. Occurrence of potential bacterial pathogens in sputum of stable COPD patients and during AECOPD, as measured by real-time qualitative PCR/ quantitative PCR and compared to data from bacteriological methods. [ Time Frame: Over the course of 1 year ]

   Including (but not necessarily limited to) H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus and P. aeruginosa.

   The proportion of sputum samples obtained at each confirmed stable/AECOPD visit and positive for specific bacterial pathogens by PCR will be computed with 95% confidence intervals.

2. Occurrence of potential bacterial and viral pathogens (overall and by species) in sputum during AECOPD by severity of AECOPD. [ Time Frame: Over the course of 1 year ]
   The proportion of sputum samples obtained at each AECOPD visit and positive for specific bacterial/viral pathogens by bacteriological methods and PCR, respectively (overall and by bacterial/viral species) will be computed with 95% confidence intervals by any severity (mild, moderate and severe).
3. Occurrence of potential bacterial and viral pathogens (overall and by species) in sputum of stable COPD patients by GOLD grade. [ Time Frame: Over the course of 1 year ]
   The proportion of sputum samples obtained at each confirmed stable visit and positive for bacterial/viral pathogens by bacteriological methods and PCR, respectively (overall and by bacterial / viral species) will be computed with 95% confidence intervals by Gold grade at enrolment.
4. Incident rate (per subject per year) of any AECOPD overall and by GOLD grade. [ Time Frame: Over the course of 1 year ]

   The following incidence rates will be computed, with 95% confidence intervals (CI):

   • All-cause AECOPD.
   • AECOPD having sputum containing bacterial pathogens found by PCR or by bacteriological methods or by both methods (overall and by, but not limited to, the following bacterial species: H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, and P. aeruginosa).

   The 95% CI of the incidence rate will be computed using a model which accounts for repeated events. The incidence rates described above will also be computed for mild, moderate severe AECOPD and by GOLD grade at enrolment.

5. Number of mild, moderate or severe AECOPD overall and by GOLD grade. [ Time Frame: Over the course of 1 year ]

   Classification of severity according to the intensity of medical intervention required:

   • mild: controlled with an increase in dosage of regular medications;
   • moderate: requires treatment with systemic corticosteroids and/ or antibiotics;
   • severe: requires hospitalisation.
6. Number of days of AECOPD episodes overall and by AECOPD severity. [ Time Frame: Over the course of 1 year ]
   Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the number of days of AECOPD episodes will be presented.
7. COPD assessment test (CAT) score in stable COPD patients and during AECOPD. [ Time Frame: Over the course of 1 year ]
   Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the CAT scores will be tabulated at each respective visit.
8. St. George's Respiratory Questionnaire (SGRQ-C) score in stable COPD patients. [ Time Frame: Over the course of 1 year ]
   Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the SGRQ-C scores will be tabulated at each respective visit.
9. Forced expiratory volume in 1 second (FEV1%) of predicted normal value in stable COPD patients. [ Time Frame: At Pre-Month 0 and Month 12 ]

   The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator FEV1.

   Summary statistics (mean, median, standard deviation, maximum and minimum) on post bronchodilator FEV1% of predicted normal value will be tabulated at each respective visit.

10. Assessment of the Healthcare utilization. [ Time Frame: Over the course of 1 year ]
    Healthcare use for each COPD patient will be obtained through review of the subject's medical record (aided by subject self-reporting). Healthcare utilisation includes all unscheduled visits to a physician office, visits to urgent care, visits to emergency department, and hospitalizations.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of electronic Diary Card, sputum sampling, pre- and post-bronchodilator spirometry, return for follow-up visits).
• Written informed consent obtained from the subject.
• Male or female aged 40 years or older at the time of enrolment.
• Confirmed diagnosis of moderate to very severe COPD based on post-bronchodilator spirometry (i.e. forced expiratory volume in 1 second [FEV1] over forced vital capacity [FVC] ratio [FEV1/ FVC] < 0.7 and FEV1 < 80% predicted [GOLD grades 2, 3 and 4].

• Stable COPD patient* with documented history** (e.g. medical record verification) of at least 1 moderate or severe AECOPD within the 12 months before study entry.

  • Patient for whom the last episode of AECOPD is resolved for at least 30 days at the time of study entry.

    • Note: A documented history of a COPD exacerbation (e.g., medical record verification) is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable.
• Current or former tobacco smoker (cigarette) with a smoking history of ≥ 10 pack-years OR a subject exposed to biomass smoke for ≥ 20 years.
• Able to provide a sputum sample at Screening Visit.

Exclusion Criteria:

• Diagnosed with a respiratory disorder other than COPD (such as sarcoidosis, active tuberculosis or receiving tuberculosis treatment, clinically significant bronchiectasis, lung fibrosis, pulmonary embolism, pneumothorax, lung cancer diagnosed within the previous 5 years, current primary diagnosis of asthma in the opinion of the investigator), or chest X-ray revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD*. Subjects with allergic rhinitis do not need to be excluded and may be enrolled at the discretion of the investigator.

  • A chest X-ray must be taken at Screening Visit, if no chest X-ray taken within the previous 3 months is available.
• Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.
• Undergone or has had lung surgery 12 months before, or plans to have lung surgery 12 months after, study entry.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Received chemotherapy within the 12 months before study entry.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/ product (pharmaceutical product or device).
• Administration of antibiotics within 1 month of study entry OR continuous administration of antibiotics (defined as more than 30 days in total) within 90 days before study entry.
• Systemic administration of corticosteroids for more than 14 consecutive days within 90 days prior to informed consent.
• Contraindication for spirometry testing (such as recent eye surgery, recent thoracic or abdominal surgery procedures, unstable cardiovascular status, recent myocardial infarction or pulmonary embolism).
• Psychiatric illness or any other condition that interferes with the ability to understand the study procedures.
• Pregnant female.

Contacts and Locations

Locations

Hong Kong

GSK Investigational Site

Kowloon, Hong Kong

GSK Investigational Site

Lai Chi Kok, Hong Kong

GSK Investigational Site

Shatin, Hong Kong

Korea, Republic of

GSK Investigational Site

Bucheon, Korea, Republic of, 420-717

GSK Investigational Site

Gangwon-do, Korea, Republic of, 26426

GSK Investigational Site

Incheon, Korea, Republic of, 403-720

GSK Investigational Site

Seoul, Korea, Republic of, 03312

GSK Investigational Site

Seoul, Korea, Republic of, 156-755

Philippines

GSK Investigational Site

Iloilo, Philippines, 5000

GSK Investigational Site

Jaro, Iloilo City, Philippines, 5000

GSK Investigational Site

Manila, Philippines, 1000

GSK Investigational Site

Manila, Philippines, 1014

GSK Investigational Site

Marilao, Bulacan, Philippines, 3019

Taiwan

GSK Investigational Site

Changhua, Taiwan, 500

GSK Investigational Site

Keelung, Taiwan, 20401

GSK Investigational Site

Taichung, Taiwan, 40201

GSK Investigational Site

Taichung, Taiwan, 404

GSK Investigational Site

Taichung, Taiwan, 40705

GSK Investigational Site

Taipei, Taiwan, 100

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03151395
• Other Study ID Numbers: 201112
• First Posted: May 12, 2017
• Last Update Posted: April 27, 2020
• Last Verified: April 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

COPD; AECOPD; GOLD (Global Initiative for Chronic Obstructive Lung Disease); Asia Pacific

Additional relevant MeSH terms:

Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiration Disorders; Respiratory Tract Diseases; Lung Diseases