Scandinavian Cystic Fibrosis Azithromycin Study

March 13, 2014 updated by: Christine Hansen, Rigshospitalet, Denmark

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • CF-centre Skejby, Skejby Sygehus, Brendstrupgaardsvej 100
      • Copenhagen, Denmark, 2100
        • CF-centre Copenhagen, Rigshospitalet, Blegdamsvej 9
  • Norway
      • Bergen, Norway, 5021
        • CF-centre Bergen, Haukeland Universitetssykehus
      • Oslo, Norway, 0407
        • CF-centre Oslo, Ullevaal Universitetssykehus
  • Sweden
      • Göteborg, Sweden, 416 85
        • CF-centre Göteborg, Drottning Silvias barn- och ungdomssjukhus
      • Lund, Sweden, 221 85
        • CF-centre Lund, Universitetssjukhuset i Lund
      • Stockholm, Sweden, 141 86
        • CF-centre Stockholm, Karolinska Universitetssjukhuset, Huddinge
      • Uppsala, Sweden, 751 85
        • CF-centre Uppsala, Akademiska Barnsjukhuset

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • Project number HSA06-20/1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa
Time Frame: up to 5 years
up to 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Clinical condition of the patients (height, weight and lung function)
Time Frame: up to 5 years
up to 5 years
Bacteriological examination of Pseudomonas aeruginosa (phenotype, resistance)
Time Frame: 5 years
5 years
Genotyping of Pseudomonas aeruginosa using Pulsed Field Gel Electrophoresis (re-infection caused by identical or new strain)
Time Frame: 5 years
5 years
Specific, precipitating pseudomonas-antibodies (establishment of chronic infection)
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Cystic Fibrosis Foundation

Investigators

  • Principal Investigator: Niels Hoiby, Prof.M.D.DSc, Department of Clinical Microbiology, Rigshospitalet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

December 14, 2006

First Submitted That Met QC Criteria

December 14, 2006

First Posted (Estimate)

December 15, 2006

Study Record Updates

Last Update Posted (Estimate)

March 14, 2014

Last Update Submitted That Met QC Criteria

March 13, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZI/SCAND/01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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