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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Tobramycin solution for inhalation 300 mg

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic fibrosis

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Tobramycin 300 mg for 28 days

Tobramycin 300 mg for 56 days

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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).

Full Information

NCT ID

NCT00391976

First Posted

October 19, 2006

Last Updated

July 29, 2011

Sponsor

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT00391976

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2011

Overall Recruitment Status

Completed

Study Start Date

November 2003 (undefined)

Primary Completion Date

January 2008 (Actual)

Study Completion Date

January 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Novartis

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

Cystic fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

123 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tobramycin 300 mg for 28 days

Arm Type

Experimental

Arm Description

Arm Title

Tobramycin 300 mg for 56 days

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tobramycin solution for inhalation 300 mg

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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 Outcome Measure Information:

Title

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

Description

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.

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

Number of Participants Hospitalized for Pulmonary Exacerbations

Description

Time Frame

From Baseline to end of study (27 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Accepts Healthy Volunteers

Eligibility Criteria

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: 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. 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Felix Ratjen

Organizational Affiliation

Royal Victoria Infirmary

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

19996339

Citation

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.

Results Reference

derived

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

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