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

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00391976

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Tobramycin solution for inhalation 300 mg	Phase III

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

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cough Cystic Fibrosis

Drug Information available for: Tobramycin Tobramycin sulfate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Time to Recurrence of Pseudomonas (P.) Aeruginosa (Any Genotype) in Sputum or Deep Throat Cough Swab [ 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) ] [ Designated as safety issue: No ]
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 [ Time Frame: From 1 month after the end of treatment until the end of the study (Month 27) ] [ Designated as safety issue: No ]
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 Frame: From 1 month after the end of treatment until the end of the study (Month 27) ] [ Designated as safety issue: No ]
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 [ Time Frame: From Baseline to the final visit (end of the study, Month 27) ] [ Designated as safety issue: No ]
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 [ Time Frame: From Baseline to end of study (27 months) ] [ Designated as safety issue: No ]
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).

Enrollment:	123
Study Start Date:	November 2003
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tobramycin 300 mg for 28 days 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 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.
Experimental: Tobramycin 300 mg for 56 days 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 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.

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.

Eligibility

Ages Eligible for Study:	6 Months and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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:
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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00391976

Sponsors and Collaborators

Novartis

Investigators

Principal Investigator:

Felix Ratjen

Royal Victoria Infirmary

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2009 Dec 8.

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00391976 History of Changes
Other Study ID Numbers:	CTBM100B2301
Study First Received:	October 19, 2006
Results First Received:	May 18, 2011
Last Updated:	July 29, 2011
Health Authority:	Austria: Agency for Health and Food Safety; Germany: Federal Institute for Drugs and Medical Devices; Spain: Spanish Agency of Medicines; France: Afssaps - French Health Products Safety Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency; Italy: National Institute of Health; Netherlands: Medicines Evaluation Board (MEB); Portugal: National Pharmacy and Medicines Institute

Keywords provided by Novartis:

Cystic fibrosis

Additional relevant MeSH terms:

Cystic Fibrosis
Fibrosis
Respiratory Tract Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn

Infant, Newborn, Diseases
Pathologic Processes
Infection
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012