Scandinavian Cystic Fibrosis Azithromycin Study

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Christine Hansen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00411736
First received: December 14, 2006
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

In patients with Cystic Fibrosis, recurrent airway infection caused by Pseudomonas aeruginosa ultimately leads to chronic airway infection. The purpose of this study is to determine whether supplementary low-dose azithromycin to standard inhaled colistin and oral ciprofloxacin in the treatment of intermittent pseudomonas airway-infection can postpone the next episode of intermittent pseudomonas airway-infection and prevent development of chronic airway-infection.


Condition Intervention Phase
Cystic Fibrosis
Drug: Study medication, azithromycin or placebo
Drug: Azithromycin or placebo tablets
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Supplementary Oral Azithromycin in Treatment of Intermittent Pseudomonas Aeruginosa Colonization in CF-patients With Inhaled Colistin and Oral Ciprofloxacin; Postponing Next Isolate of Pseudomonas and Prevention of Chronic Infection. A Prospective, Double-blinded, Placebo-controlled Scandinavian Multi-centre Study.

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical condition of the patients (height, weight and lung function) [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
  • Bacteriological examination of Pseudomonas aeruginosa (phenotype, resistance) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Genotyping of Pseudomonas aeruginosa using Pulsed Field Gel Electrophoresis (re-infection caused by identical or new strain) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Specific, precipitating pseudomonas-antibodies (establishment of chronic infection) [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: May 2008
Study Completion Date: March 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Stratification group: Age under 8 years, no CF siblings at home.
Drug: Study medication, azithromycin or placebo
Granulate for syrup in the group under 8 years, 40 mg/ml. Dose: 5 mg/kg/day in one daily dose.
Other Name: Projectnumber HSA06-20/1
Experimental: B
Stratification group: Age >/= 8 years, no CF siblings at home.
Drug: Azithromycin or placebo tablets
Tablets of 250 mg, azithromycin or placebo. Dosage: 1 tablet every other day for participants with a weight less than 40 kg´s. 1 tablet every day for participants weighing 40 kg´s or more.
Other Name: Project number HSA06-20/1
Experimental: C
Stratification group: Age >/= 8 years, CF siblings at home.
Drug: Azithromycin or placebo tablets
Tablets of 250 mg, azithromycin or placebo. Dosage: 1 tablet every other day for participants with a weight less than 40 kg´s. 1 tablet every day for participants weighing 40 kg´s or more.
Other Name: Project number HSA06-20/1

Detailed Description:

Cystic Fibrosis is the most common genetic, inherited, deadly disease in caucasians. The disease is characterized by recurrent airway-infections caused by Pseudomonas aeruginosa, ultimately leading to chronic airway-infection, which is the main cause of the increased morbidity and mortality seen in this disease.

P. aeruginosa has the ability to change to mucoid phenotype - producing alginate and growing in biofilm, which protects the microorganisms from antibiotics and leukocytes. The change in phenotype is seen as chronic infection is established and eradication becomes impossible. Treatment with long-term, low-dose azithromycin in chronically infected CF-patients can improve the clinical condition of the patients. The exact mechanism for this is not known, but is possibly a combination of anti-inflammatory effects and the ability of azithromycin to inhibit alginate-production. Inhibition of biofilm-formation leaves the bacteria more susceptible to the actions of antibiotics and leukocytes.

Prior to establishment of chronic infection, recurrent, intermittent colonization of the airways with non-mucoid P. aeruginosa is seen. Intermittent infections can be treated using a combination of antibiotics, thereby postponing the next episode of airway-infection with P. aeruginosa.

The purpose of this study is to clarify wether supplementary azithromycin in the treatment of intermittent pseudomonas-infection in CF-patients can lead to further postponement of next pseudomonas-colonization and maybe prevent development of chronic infection. This is done in a randomised, double-blinded, placebo-controlled multicentre study.

2 treatments will be compared:

  1. Inhaled colistin and oral ciprofloxacin in combination with oral azithromycin
  2. Inhaled colistin and oral ciprofloxacin in combination with oral placebo.

The treatment will be given for 3 weeks, and the primary end-point is the time until next colonization with P. aeruginosa in the airways of the patients, comparing the 2 treatment-groups.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Cystic Fibrosis based on genotype and/or positive sweat-test
  • Written informed consent based on written and spoken information
  • No chronic airway-infections with Gram-negative bacteria
  • Fertile, sexually active women must use contraception (p-pills, IUD or other methods with a similar Pearl-index) when participating in the study

Exclusion Criteria:

  • P. aeruginosa in airway secretions obtained less than 3 months prior to inclusion
  • Chronic infection of the airways caused by Gram-negative bacteria (Burkholderia species, Achromobacter xylosoxidans, Pandorea apista or Stenotrophomonas maltophilia)
  • Chronic infection of the airways caused by P. aeruginosa (chronic infection is defined by continuing growth of the microorganism for 6 months and/or an increase in specific, precipitating antibodies to a level of at least 2)
  • Previous infection with a strain of P. aeruginosa resistant to ciprofloxacin or colistin
  • Previous participation in a pseudomonas-vaccination-study
  • Patients younger than 1 year
  • Pregnant or lactating women, or sexually active women unwilling to use safe contraception (p-pills, IUD or method with similar Pearl-index) when participating in the study
  • Severe insufficiency of the liver or kidneys as judged by the local investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411736

Locations
Denmark
CF-centre Skejby, Skejby Sygehus, Brendstrupgaardsvej 100
Aarhus N, Denmark, 8200
CF-centre Copenhagen, Rigshospitalet, Blegdamsvej 9
Copenhagen, Denmark, 2100
Norway
CF-centre Bergen, Haukeland Universitetssykehus
Bergen, Norway, 5021
CF-centre Oslo, Ullevaal Universitetssykehus
Oslo, Norway, 0407
Sweden
CF-centre Göteborg, Drottning Silvias barn- och ungdomssjukhus
Göteborg, Sweden, 416 85
CF-centre Lund, Universitetssjukhuset i Lund
Lund, Sweden, 221 85
CF-centre Stockholm, Karolinska Universitetssjukhuset, Huddinge
Stockholm, Sweden, 141 86
CF-centre Uppsala, Akademiska Barnsjukhuset
Uppsala, Sweden, 751 85
Sponsors and Collaborators
Rigshospitalet, Denmark
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Niels Hoiby, Prof.M.D.DSc Department of Clinical Microbiology, Rigshospitalet
  More Information

Publications:

Responsible Party: Christine Hansen, Medical doctor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT00411736     History of Changes
Other Study ID Numbers: AZI/SCAND/01
Study First Received: December 14, 2006
Last Updated: March 13, 2014
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Medicines Agency
Norway: Norwegian Medicines Agency
Norway:National Committee for Medical and Health Research Ethics
Sweden: Medical Products Agency
Sweden: Swedish National Council on Medical Ethics

Keywords provided by Rigshospitalet, Denmark:
Cystic Fibrosis
Pseudomonas aeruginosa
Azithromycin
Intermittent pulmonary infection

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014