Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis (CCTOBI)

Prospective Randomized Trial Comparing Oral Ciproxin Plus Inhaled Colistin With Tobramycin for Inhalation for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis.

Treatment of new Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) can postpone chronic infection. Aim of the study: compare 2 Pa eradication regimens in children with new Pa infection.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: oral ciprofloxacin plus inhaled colistin; Drug: TOBI

Detailed Description

Methods: CF children (0-18 years) with a new isolation of Pa from the airway were randomized to tobramycin inhalation solution (TOBI® 2x300 mg for 28 days) (TIS) or inhaled colistimethate sodium (Colistineb® 2x2 mill U daily) plus oral ciprofloxacin (30mg/kg/day) for 3 months (CC). The primary outcome was eradication at end of treatment. Secondary outcome parameters were time to Pa relapse, total and Pa specific IgG, FEV1, BMI and Pa status.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Department of pediatrics, CF center Uuiversity Hospital Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of CF (clinical signs consistent with CF and a sweat chloride > 60 mEq/l by quantitative pilocarpine iontophoresis and/or two CF causing mutations identified)
• age 0 to 18 years old at time of inclusion
• 'First' or 'new Pa infection' defined as 'first Pa isolation ever' or 'isolation of Pa from the airway (sputum, throat swab or BAL) after a Pa free interval of at least 6 months and documented with at least 3 negative cultures'.

Exclusion Criteria:

• chronic Pa infection defined according to the Leeds criteria[17]
• pulmonary exacerbation needing IV AB treatment at time of new Pa isolate
• Pa isolation at time of CF diagnosis
• patient already on an antipseudomonal antibiotic
• interval between positive culture and start of treatment > 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ciproxin-inhaled Colistin; oral ciprofloxacin (30mg/kg/day) plus inhaled colistimethate sodium (Colistineb® 2x2 mill U daily) for 3 months	Drug: oral ciprofloxacin plus inhaled colistin; oral ciprofloxacin (30mg/kg/day divided in 2 doses) for 3 months (CC) plus inhaled colistimethate sodium(Colistineb® 2x2 mill U daily); Other Names: Ciproxin ® - ciprofloxacin; Colistineb ®
ACTIVE_COMPARATOR: Tobramycine for inhalation (TIS); tobramycin inhalation solution (TOBI® 2x300 mg) for 28 days	Drug: TOBI; tobramycin inhalation solution (TOBI® 2x300 mg) for 28 days; Other Names: TOBI® - tobramycin inhalation solution (TIS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pseudomonas aeruginosa eradication at the end of the treatment.	sucessful eradication is defined as negative airway culture for P aeruginosa and end of study drug which is after 3 months for ciproxin-colistin (CC) and after 1 months for tobramycin for inhalation (TIS)	end of study drug treatment ie 3 months for CC and at 1 months for TIS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P aeruginosa eradication at 6 months after study entry	negative airway cultures for P aeruginosa up to 6 months after start of study drug	6 months
time to new Pa positive culture (= relapse)	Time to first new P aeruginosa positive airway culture (expressed in months starting from end of study drug)	1 year
change from baseline FEV1% pred, IgG z score, BMI z score was followed	Evolution of lung function (expressed as FEV1% pred), total IgG and nutritional status (expressed as BMI z score) from start of study up to 1 year	1 year
Antibody titer for specific anti Pseudomonas antibodies	Pa antibodies (ELISA St Ag 1-17 )were measured at baseline and at 1 year follow-up	1 year
P aeruginosa infection status	P aeruginosa infection status was reported as 'Free off', 'Intermittent' or 'Chronic' according to the Leeds criteria after 1 and 2 years. (ref Leeds criteria: Lee TW, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003;2(1):29-34)	1 year
P aeruginosa infection status	P aeruginosa infection status was reported as 'Free off', 'Intermittent' or 'Chronic' according to the Leeds criteria after 1 and 2 years. (ref Leeds criteria: Lee TW, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003;2(1):29-34)	2 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Marijke J Proesmans, MD, PhD, Dep pediatrics University Hospital Leuven Belgium

Publications and helpful links

General Publications

• Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004197. doi: 10.1002/14651858.CD004197.pub3.

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 21, 2011
• First Posted (ESTIMATE): July 22, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 4, 2011
• Last Update Submitted That Met QC Criteria: August 3, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: cystic fibrosis- P aeruginosa- eradication-child
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin; Tobramycin; Colistin
• Other Study ID Numbers: MP1