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

Cystic Fibrosis Clinical Trial

— ELITE  

Official title:

The Microbiologic Efficacy and Safety of Two Treatment Regimens of Inhaled Tobramycin Nebuliser Solution (TNS) for the Treatment of Early Onset Pseudomonas Aeruginosa Lower Respiratory Tract Infection in Subjects With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00391976
• Other study ID #: CTBM100B2301
• Status: Completed
• Phase: Phase 3
• First received: October 19, 2006
• Last updated: July 29, 2011
• Start date: November 2003
• Est. completion date: January 2008

Study information

• Verified date: July 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyGermany: Federal Institute for Drugs and Medical DevicesSpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyItaly: National Institute of HealthNetherlands: Medicines Evaluation Board (MEB)Portugal: National Pharmacy and Medicines Institute
• Study type: Interventional

Clinical Trial 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.

Description:

This was a multi-center, open-label, two-arm, randomized study. All patients diagnosed with CF and who fulfilled the criteria for early infection with P. aeruginosa initially received tobramycin 300 mg twice a day for 28 days. At the end of the 28-day treatment period, patients who met the inclusion criteria and none of the additional exclusion criteria were randomized in a 1:1 ratio to either receive an additional 28 days of treatment with tobramycin 300 mg twice a day (56-day group) or to stop study medication (28-day group).

All randomized patients had regular study visits until a positive P. aeruginosa sample was obtained. Once P. aeruginosa had recurred, the patient entered a follow-up phase where minimal information was collected for 27 months. During the follow-up phase, patients were treated according to their physicians' discretion.

Patients who started treatment with tobramycin but were not randomized (i.e. due to a positive antibody test) and followed up during routine clinic visits. They were allowed to continue their 28-day treatment period and afterwards be treated according to their physicians' discretion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months and older

Eligibility

Inclusion criteria:

• Male or female patients = 6 months old

• Diagnosis of cystic fibrosis (CF) based upon the following historical criteria performed prior to study participation:

1. confirmed sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis (at least 2 tests), OR

2. 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:

1. first infection defined by the first P. aeruginosa isolated from sputum or deep throat cough swab culture, OR

2. 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

3. 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.

Exclusion criteria:

• 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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Respiratory Tract Infections

Intervention

Drug:
• Tobramycin solution for inhalation 300 mg
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Percentage of Patients With Pseudomonas (P.) Aeruginosa Eradicated From Deep Throat Cough Swab or Sputum	One month after the end of treatment was Day 56 (Month 2) for the 28-day treatment group and Month 3 for the 56-day treatment group.	From 1 month after the end of treatment until the end of the study (Month 27)	No
Secondary	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	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.	From 1 month after the end of treatment until the end of the study (Month 27)	No
Secondary	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	The percentage of patients with changes in tobramycin MIC values from Baseline to the final visit could not be compared as there was insufficient data.	From Baseline to the final visit (end of the study, Month 27)	No
Secondary	Number of Participants Hospitalized for Pulmonary Exacerbations	Core study defined as from Baseline through to one month after the end of treatment (Day 56 for the 28-day treatment group and Month 3 for the 56-day treatment group). Follow-up phase began at the end of the core study through to the end of the study (Month 27).	From Baseline to end of study (27 months)	No