Cystic FibrosisPhase 3ELITENCT00391976
Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis
A Phase 3 study testing Tobramycin solution for inhalation 300 mg in people with Cystic Fibrosis, run by Novartis.
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… Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Tobramycin solution for inhalation 300 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- No sites listed yet
- Study dates
- Nov 2003to Jan 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
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- 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).
About this study
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
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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Tobramycin solution for inhalation 300 mg
- Keywords
- Cystic fibrosis
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobramycin solution for inhalation 300 mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Tobramycin solution for inhalation 300 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: From Baseline to the final visit (end of the study, Month 27)
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).
Measured: From Baseline to end of study (27 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2006 (estimated)
- Study startNov 2003
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Felix Ratjen, Principal investigator, Royal Victoria Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00391976
- Sponsor's protocol ID
- CTBM100B2301
- Acronym
- ELITE
- Status last verified
- Jul 2011
- First submitted
- 19 Oct 2006
- Last updated
- 29 Aug 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 19996339
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00391976
- Acronym / sponsor ID
- ELITE / CTBM100B2301
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Nov 2003
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 25 Oct 2006 (estimated)
- Results
- Posted 29 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tobramycin 300 mg for 28 days | Experimental | Drug: Tobramycin solution for inhalation 300 mgPatients 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. |
| Tobramycin 300 mg for 56 days | Experimental | Drug: Tobramycin solution for inhalation 300 mgPatients 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. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female patients ≥ 6 months old
- Diagnosis of cystic fibrosis (CF) based upon the following historical criteria performed prior to study participation:
- First or early lower respiratory tract infection with Pseudomonas (P.) aeruginosa documented by either of the following:
- Written informed consent by the patient and/or parent/legal guardian according to local country regulations.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tobramycin solution for inhalation 300 mgTobramycin 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. | Drug | Tobramycin 300 mg for 28 days, Tobramycin 300 mg for 56 days |
Primary outcome
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)
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.
4 secondary outcomes
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)
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)
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)
Number of Participants Hospitalized for Pulmonary Exacerbations
Time frame: From Baseline to end of study (27 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19996339Ratjen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Felix Ratjen principal investigator
Royal Victoria Infirmary
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tobramycin solution for inhalation 300 mg in people with Cystic Fibrosis, run by Novartis.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00391976, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2011.