Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis

NCT00391976 | Completed Phase 3 Results

• 1 other identifier: CTBM100B2301
• Study Type: interventional
• Target: 123
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study assessed time to recurrence of infection with Pseudomonas aeruginosa following treatment of the initial infection with tobramycin nebuliser solution. The safety profile of the initial tobramycin treatment was assessed during the first 3 months of the study and patients were followed until the end of the study, month 27.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis

Outcome Measures

Primary Outcomes (1)

• Time to Recurrence of Pseudomonas (P.) Aeruginosa (Any Genotype) in Sputum or Deep Throat Cough Swab

  Microbiological samples were obtained from sputum or by deep throat cough swab technique. Time to recurrence was defined as the time between the visit at 1 month after the end of treatment (when eradication was confirmed) and the time of the first positive culture with any genotype of P. aeruginosa. Time zero was Day 56 (Month 2) for the 28-day treatment group and Month 3 for the 56-day treatment group. Kaplan-Meier estimates were used.

  From 1 month after the end of treatment (Day 56 for the 28-day treatment group and Month 3 for the 56-day treatment group) until the end of the study (Month 27)

Secondary Outcomes (4)

• Percentage of Patients With Pseudomonas (P.) Aeruginosa Eradicated From Deep Throat Cough Swab or Sputum

  From 1 month after the end of treatment until the end of the study (Month 27)

• Time to Recurrence of Pseudomonas (P.) Aeruginosa (New or Same Genotype) in Sputum or Deep Throat Cough Swab Based on Confirmatory Assessment by the Central Laboratory

  From 1 month after the end of treatment until the end of the study (Month 27)

• Percentage of Patients With Pseudomonas (P.) Aeruginosa Having an Increased, Decreased, or Unchanged Tobramycin Minimum Inhibitory Concentration (MIC) Value at the Final Visit Compared to Baseline

  From Baseline to the final visit (end of the study, Month 27)

• Number of Participants Hospitalized for Pulmonary Exacerbations

  From Baseline to end of study (27 months)

Study Arms (2)

Tobramycin 300 mg for 28 days

EXPERIMENTAL

Patients inhaled tobramycin 300 mg bis in die (bid, twice a day) for 28 days using the PARI LC PLUS™ jet nebulizer and a suitable compressor. The 2 daily doses were taken approximately 12 hours apart and no less than 6 hours apart.

Drug: Tobramycin solution for inhalation 300 mg

Tobramycin 300 mg for 56 days

EXPERIMENTAL

Patients inhaled tobramycin 300 mg bis in die (bid, twice a day) for 56 days using the PARI LC PLUS™ jet nebulizer and a suitable compressor. The 2 daily doses were taken approximately 12 hours apart and no less than 6 hours apart.

Drug: Tobramycin solution for inhalation 300 mg

Interventions

Tobramycin solution for inhalation 300 mg DRUG

Tobramycin solution for inhalation was supplied in 5 mL liquid-filled low-density polyethylene ampoules containing 300 mg tobramycin. Patients used a nebulizer to inhale the contents of the ampoules.

Tobramycin 300 mg for 28 days; Tobramycin 300 mg for 56 days

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 6 months old
• Diagnosis of cystic fibrosis (CF) based upon the following historical criteria performed prior to study participation:
• confirmed sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis (at least 2 tests), OR
• genotype with two identifiable mutations consistent with CF.
• First or early lower respiratory tract infection with Pseudomonas (P.) aeruginosa documented by either of the following:
• first infection defined by the first P. aeruginosa isolated from sputum or deep throat cough swab culture, OR
• P. aeruginosa from sputum or deep throat cough swab culture following at least 1 year of negative cultures (documented with at least 4 negative cultures during this year and no positive cultures) and no anti-pseudomonal treatment during this 1-year period, OR
• P. aeruginosa from sputum or deep throat cough swab culture following at least 2 years of negative cultures (documented with at least 2 negative cultures per year and no positive cultures) and no anti-pseudomonal treatment during this 2-year period.
• Written informed consent by the patient and/or parent/legal guardian according to local country regulations.

You may not qualify if:

• History of aminoglycoside hypersensitivity or adverse reaction to inhaled aminoglycoside.
• Signs and symptoms of acute pulmonary disease, eg, pneumonia, pneumothorax.
• Administration of any investigational drug within 30 days prior to enrollment.
• Administration of loop diuretics within 7 days prior to study drug administration.
• Personal/family history of abnormal hearing, other than typical hearing loss associated with the aging process.
• Abnormal result from an audiology testing (defined as either a unilateral pure-tone audiometry test showing a threshold elevation \> 20 decibels \[dB\] at any frequency across the frequency range 0.25-8 kHz or the absence of emission at the evoked otoacoustic emission test).
• Positive urine pregnancy test at Day 1 (Baseline) for all female patients who have reached menarche.
• Use of macrolide antibiotics as a maintenance therapy for 12 or more days during the 28 days prior to Baseline.
• Antibody titers ≥ 1000 for any of the 3 P. aeruginosa exoenzymes: Exotoxin A, alkaline protease, or elastase (status to be determined between Baseline and Day 28).

Sponsors & Collaborators

• Novartis: lead

Related Publications (1)

• Ratjen F, Munck A, Kho P, Angyalosi G; ELITE Study Group. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax. 2010 Apr;65(4):286-91. doi: 10.1136/thx.2009.121657. Epub 2009 Dec 8.

  PMID: 19996339 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Inhalation

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

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Felix Ratjen

  Royal Victoria Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 19, 2006
• First Posted: October 25, 2006
• Study Start: November 1, 2003
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: August 29, 2011
• Results First Posted: August 29, 2011

Record last verified: 2011-07