Macrolide Maintenance Therapy in Chronic Obstructive Pulmonary Disease

COPD Clinical Trial

— COLUMBUS  

Official title:

Influence of Macrolide Maintenance Therapy and Bacterial Colonisation on Exacerbation Frequency and Progression of COPD, a Randomized Double-blind Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00985244
• Other study ID #: Amphia-ABR29500
• Secondary ID: 2009-015857-19
• Status: Completed
• Phase: N/A
• First received: September 25, 2009
• Last updated: June 25, 2013
• Start date: May 2010
• Est. completion date: June 2013

Study information

• Verified date: June 2013
• Source: Amphia Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

To assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the preceding year of inclusion can decrease the exacerbation rate in the year of treatment.

Description:

COPD is characterized by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response.One of the hypothesis for persistent airway inflammation is that the presence of recurrent infections is responsible for this condition.

Macrolide antibiotics have a bacteriostatic as well as anti-inflammatory properties. This clinical trial will investigate whether maintenance treatment with macrolide antibiotics during 1 year in people with 3 or more exacerbations in the preceding year of inclusion can decrease the exacerbation rate in that same year of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of COPD according to GOLD criteria (FEV1/FVC<70%), classification into GOLD I (FEV1 70-100% predicted), GOLD II (FEV1 50-70% predicted), GOLD III (FEV1 30- 50% predicted) or GOLD IV (FEV1 = 30% predicted)

• Age = 18 years

• Three or more exacerbations of COPD in one year for which a course of prednisone and/or antibiotic therapy was started

• Clinically stable during 1 month. Patients have to be free of COPD exacerbation or respiratory tract infection within a month prior to involvement in the study and they should not have received a high dose of systemic glucocorticoids or antibiotics in this period

• Informed consent

Exclusion Criteria:

• Use of antibiotics or high dose of systemic steroids within a month prior to involvement in the study.

• Addition of inhalation steroids to the patient's therapy regimen, shortly before entering the study.

• Pregnant or lactating women.

• Allergy to macrolides.

• Liver disease (alanine transaminase and/or aspartate transaminase levels 2 or more times the upper limit of normal).

• Asthma, defined as episodic symptoms of airflow obstruction which is reversible with bronchodilators, assessed with lung function testing.

• Presence of a malignancy which is clinically active.

• Bronchiectasis.

• Malignancy of any kind for which the subject is under treatment or is being monitored as part of follow up after treatment.

• Heart failure.

• Use of drugs which can adversely interact with macrolides and for which therapeutic monitoring cannot be undertaken.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• COPD
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Azithromycin
Subjects in this group will receive 3 times a week 500 mg of the antibiotic azithromycin during 1 year.
• Placebo
Persons in this group will receive 3 times a week placebo of azithromycin during 1 year.

Locations

Country	Name	City	State
Netherlands	Amphia Ziekenhuis	Breda	Noord-Brabant

Sponsors (4)

Lead Sponsor	Collaborator
R.S. Djamin	Amphia Hospital, Erasmus Medical Center, Stichting Solong

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in number of exacerbations		1 year	No
Secondary	Lung function parameters (FEV1 (L), FVC (L), FRC (L), RV (L), TLC(L), IC (L), 6 minute walking distance)		Day 1. Also 3, 6, 9 and 12 months.	No
Secondary	Disease specific health related quality of life measured by St. George's Respiratory Questionnaire (SGRQ)		Day 1. Also 3, 6, 9 and 12 months. In case of an exacerbation.	No
Secondary	Indication of anxiety and depression by Hospital Anxiety Depression Scale (HADS)		Day 1. Also 3, 6, 9 and 12 months.	No
Secondary	Microbiology of sputum (culture and PCR).		Day 1. Also 3, 6, 9 and 12 months. In case of an exacerbation of COPD.	No
Secondary	Measurement of inflammatory markers in sputum and serum.		Day 1. Also 3, 6, 9 and 12 months. In case of an exacerbation of COPD.	No
Secondary	Adverse events of treatment.		Day 1. Also 3, 6, 9 and 12 months. Whenever adverse events occur.	Yes
Secondary	Length of hospital stay.		Whenever admission to hospital is required for an exacerbation of COPD.	No
Secondary	Time till next exacerbation.		Whenever an exacerbation of COPD occurs.	No
Secondary	Assess type D personality by DS-14 questionnaire.		Day 1 and month 12.	No
Secondary	Generic health status measured by 12-Item Short Form Health Survey (SF-12).		Day 1, month 3, 6, 9 and 12. In case of an exacerbation.	No
Secondary	Decrease in percentage of clinical versus outdoor department exacerbations.		Month 12.	No
Secondary	Effect of maintenance macrolides on intestinal bacterial restistancy patterns		Day 1, month 6 and month 12	No
Secondary	Serology and PCR for atypical microorganisms in serum		day 1. In case of an exacerbation.	No
Secondary	Intestinal bacterial resistance patterns	Rectal swabs will be tested for bacterial resistance patterns and change in rectal flora as a result of maintenance azithromycin.	Day 1, month 6 and month 12	No