Macrolide Maintenance Therapy in Chronic Obstructive Pulmonary Disease

NCT00985244 | Completed DMC

• 2 other identifiers: Amphia-ABR295002009-015857-19
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COPD

Keywords

COPD; COPD exacerbation; macrolide; diseae progression; bacterial colonisation

Outcome Measures

Primary Outcomes (1)

• Reduction in number of exacerbations

  1 year

Secondary Outcomes (14)

• 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.

• 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.

• Indication of anxiety and depression by Hospital Anxiety Depression Scale (HADS)

  Day 1. Also 3, 6, 9 and 12 months.

• Microbiology of sputum (culture and PCR).

  Day 1. Also 3, 6, 9 and 12 months. In case of an exacerbation of COPD.

• Measurement of inflammatory markers in sputum and serum.

  Day 1. Also 3, 6, 9 and 12 months. In case of an exacerbation of COPD.

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

Subjects in this group will receive 3 times a week 500 mg of the antibiotic azithromycin

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

Subjects in this group will receive 3 times a week placebo

Drug: Placebo

Interventions

Azithromycin DRUG

Subjects in this group will receive 3 times a week 500 mg of the antibiotic azithromycin during 1 year.

Also known as: Zithromax, Azitrocin, Ultreon, Azadose, Sumamed, Azacleus, Nuzaca, Toraseptol, Vinzam, Zentavion

Azithromycin

Placebo DRUG

Persons in this group will receive 3 times a week placebo of azithromycin during 1 year.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• R.S. Djamin: lead
• Erasmus Medical Center: collaborator
• Stichting Solong: collaborator
• Amphia Hospital: collaborator

Study Sites (1)

Amphia Ziekenhuis

Breda, North Brabant, 4818 CK, Netherlands

Location

Related Publications (3)

• Djamin RS, Talman S, Schrauwen EJA, von Wintersdorff CJH, Wolffs PF, Savelkoul PHM, Uzun S, Kerstens R, van der Eerden MM, Kluytmans JAJW. Prevalence and abundance of selected genes conferring macrolide resistance genes in COPD patients during maintenance treatment with azithromycin. Antimicrob Resist Infect Control. 2020 Jul 28;9(1):116. doi: 10.1186/s13756-020-00783-w.

  PMID: 32723393 DERIVED

• Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van't Veer NE, Ermens AA, Pelle AJ, Hoogsteden HC, Aerts JG, van der Eerden MM. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014 May;2(5):361-8. doi: 10.1016/S2213-2600(14)70019-0. Epub 2014 Apr 15.

  PMID: 24746000 DERIVED

• Uzun S, Djamin RS, Kluytmans J, Van't Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. doi: 10.1186/1745-6215-13-82.

  PMID: 22682323 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Joachim Aerts, MD, PhD

  Amphia ziekenhuis

  STUDY DIRECTOR

• Menno van der Eerdem, MD, PhD

  Erasmus Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 25, 2009
• First Posted: September 28, 2009
• Study Start: May 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 26, 2013

Record last verified: 2013-06

Locations

NL (1)