Scandinavian Cystic Fibrosis Azithromycin Study
Information source: Rigshospitalet, Denmark
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis
Intervention: Study medication, azithromycin or placebo (Drug); Azithromycin or placebo tablets (Drug)
Phase: Phase 4
Sponsored by: Rigshospitalet, Denmark
Official(s) and/or principal investigator(s):
Niels Hoiby, Prof.M.D.DSc, Principal Investigator, Affiliation: Department of Clinical Microbiology, Rigshospitalet
Christine R Hansen, M.D., Phone: +45 35 45 47 60, Email: email@example.com
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
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.
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Primary outcome: Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa
Clinical condition of the patients (height, weight and lung function)
Bacteriological examination of Pseudomonas aeruginosa (phenotype, resistance)
Genotyping of Pseudomonas aeruginosa using Pulsed Field Gel Electrophoresis (re-infection caused by identical or new strain)
Specific, precipitating pseudomonas-antibodies (establishment of chronic infection)
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
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
Minimum age: 1 Year.
Maximum age: N/A.
- 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
- 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
- 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
- Severe insufficiency of the liver or kidneys as judged by the local investigator
Locations and Contacts
Christine R Hansen, M.D., Phone: +45 35 45 47 60, Email: firstname.lastname@example.org
CF-centre Skejby, Skejby Sygehus, Brendstrupgaardsvej 100, Aarhus N 8200, Denmark; Recruiting
Oluf Schioetz, Prof.M.D.DSc, Phone: +45 89 49 67 40, Email: email@example.com
Oluf Schioetz, Prof.M.D.DSc, Principal Investigator
CF-centre Copenhagen, Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark; Recruiting
Tacjana Pressler, M.D.DSc., Phone: +45 35 45 12 98, Email: firstname.lastname@example.org
Phone: +45 35 45 50 06
Tacjana Pressler, M.D.DSc., Principal Investigator
CF-centre Bergen, Haukeland Universitetssykehus, Bergen 5021, Norway; Not yet recruiting
Birger N Laerum, M.D., Phone: +47 55 97 32 45, Email: email@example.com
Birger N Laerum, M.D., Principal Investigator
CF-centre Oslo, Ullevaal Universitetssykehus, Oslo 0407, Norway; Recruiting
Olav-Trond Storroesten, M.D., Phone: +47 23 01 55 90, Email: firstname.lastname@example.org
Olav-Trond Storroesten, M.D., Principal Investigator
CF-centre Göteborg, Drottning Silvias barn- och ungdomssjukhus, Göteborg 416 85, Sweden; Not yet recruiting
Anders Lindblad, M.D., Phone: +46 31 34 35 624, Email: email@example.com
Anders Lindblad, M.D., Principal Investigator
CF-centre Lund, Universitetssjukhuset i Lund, Lund 221 85, Sweden; Not yet recruiting
Peter Meyer, M.D., Phone: +46 6 17 15 90, Email: Peter.Meyer@skane.se
Peter Meyer, M.D., Principal Investigator
CF-centre Stockholm, Karolinska Universitetssjukhuset, Huddinge, Stockholm 141 86, Sweden; Not yet recruiting
Lena Hjalte, M.D., Phone: +46 6 585 873 59, Email: Lena.Hjalte@karolinska.se
Lena Hjalte, M.D., Principal Investigator
CF-centre Uppsala, Akademiska Barnsjukhuset, Uppsala 751 85, Sweden; Not yet recruiting
Annika Hollsing, M.D., Phone: +46 18 61 127 60, Email: firstname.lastname@example.org
Marie Johannesson, Prof.M.D.Phd, Principal Investigator
Doring G, Conway SP, Heijerman HG, Hodson ME, Hoiby N, Smyth A, Touw DJ. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J. 2000 Oct;16(4):749-67. Review.
Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros. 2005 Aug;4 Suppl 2:49-54. Review.
Valerius NH, Koch C, Hoiby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet. 1991 Sep 21;338(8769):725-6.
Equi A, Balfour-Lynn IM, Bush A, Rosenthal M. Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial. Lancet. 2002 Sep 28;360(9338):978-84.
Gillis RJ, White KG, Choi KH, Wagner VE, Schweizer HP, Iglewski BH. Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 2005 Sep;49(9):3858-67.
Hansen CR, Pressler T, Koch C, Hoiby N. Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study. J Cyst Fibros. 2005 Mar;4(1):35-40.
Jaffe A, Francis J, Rosenthal M, Bush A. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet. 1998 Feb 7;351(9100):420. No abstract available.
Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, Coquillette S, Fieberg AY, Accurso FJ, Campbell PW 3rd; Macrolide Study Group. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003 Oct 1;290(13):1749-56.
Wolter J, Seeney S, Bell S, Bowler S, Masel P, McCormack J. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax. 2002 Mar;57(3):212-6.
Kobayashi H. Biofilm disease: its clinical manifestation and therapeutic possibilities of macrolides. Am J Med. 1995 Dec 29;99(6A):26S-30S.
Starting date: May 2008
Last updated: March 18, 2010