Scandinavian Cystic Fibrosis Azithromycin Study

NCT00411736 | Completed Phase 4 DMC

• 1 other identifier: AZI/SCAND/01
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Pseudomonas aeruginosa; Azithromycin; Intermittent pulmonary infection

Outcome Measures

Primary Outcomes (1)

• Time to next airway-colonization (re-colonization) with Pseudomonas aeruginosa

  up to 5 years

Secondary Outcomes (4)

• Clinical condition of the patients (height, weight and lung function)

  up to 5 years

• Bacteriological examination of Pseudomonas aeruginosa (phenotype, resistance)

  5 years

• Genotyping of Pseudomonas aeruginosa using Pulsed Field Gel Electrophoresis (re-infection caused by identical or new strain)

  5 years

• Specific, precipitating pseudomonas-antibodies (establishment of chronic infection)

  5 years

Study Arms (3)

A

EXPERIMENTAL

Stratification group: Age under 8 years, no CF siblings at home.

Drug: Study medication, azithromycin or placebo

B

EXPERIMENTAL

Stratification group: Age \>/= 8 years, no CF siblings at home.

Drug: Azithromycin or placebo tablets

C

EXPERIMENTAL

Stratification group: Age \>/= 8 years, CF siblings at home.

Drug: Azithromycin or placebo tablets

Interventions

Study medication, azithromycin or placebo DRUG

Granulate for syrup in the group under 8 years, 40 mg/ml. Dose: 5 mg/kg/day in one daily dose.

Also known as: Projectnumber HSA06-20/1

A

Azithromycin or placebo tablets DRUG

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.

Also known as: Project number HSA06-20/1

B; C

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (8)

CF-centre Skejby, Skejby Sygehus, Brendstrupgaardsvej 100

Aarhus N, 8200, Denmark

Location

CF-centre Copenhagen, Rigshospitalet, Blegdamsvej 9

Copenhagen, 2100, Denmark

Location

CF-centre Bergen, Haukeland Universitetssykehus

Bergen, 5021, Norway

Location

CF-centre Oslo, Ullevaal Universitetssykehus

Oslo, 0407, Norway

Location

CF-centre Göteborg, Drottning Silvias barn- och ungdomssjukhus

Gothenburg, 416 85, Sweden

Location

CF-centre Lund, Universitetssjukhuset i Lund

Lund, 221 85, Sweden

Location

CF-centre Stockholm, Karolinska Universitetssjukhuset, Huddinge

Stockholm, 141 86, Sweden

Location

CF-centre Uppsala, Akademiska Barnsjukhuset

Uppsala, 751 85, Sweden

Location

Related Publications (10)

• 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. doi: 10.1034/j.1399-3003.2000.16d30.x.

  PMID: 11106223 BACKGROUND

• Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros. 2005 Aug;4 Suppl 2:49-54. doi: 10.1016/j.jcf.2005.05.018.

  PMID: 16023416 BACKGROUND

• 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. doi: 10.1016/0140-6736(91)91446-2.

  PMID: 1679870 BACKGROUND

• 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. doi: 10.1016/s0140-6736(02)11081-6.

  PMID: 12383667 BACKGROUND

• 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. doi: 10.1128/AAC.49.9.3858-3867.2005.

  PMID: 16127063 BACKGROUND

• 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. doi: 10.1016/j.jcf.2004.09.001.

  PMID: 15752679 BACKGROUND

• 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. doi: 10.1016/S0140-6736(05)78360-4. No abstract available.

  PMID: 9482305 BACKGROUND

• 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. doi: 10.1001/jama.290.13.1749.

  PMID: 14519709 BACKGROUND

• 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. doi: 10.1136/thorax.57.3.212.

  PMID: 11867823 BACKGROUND

• Kobayashi H. Biofilm disease: its clinical manifestation and therapeutic possibilities of macrolides. Am J Med. 1995 Dec 29;99(6A):26S-30S. doi: 10.1016/s0002-9343(99)80282-4.

  PMID: 8585531 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Niels Hoiby, Prof.M.D.DSc

  Department of Clinical Microbiology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor

Study Record Dates

• First Submitted: December 14, 2006
• First Posted: December 15, 2006
• Study Start: May 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: March 14, 2014

Record last verified: 2014-03

Locations

NO (2); SE (4); DK (2)