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Targeting antibiotics to pseudomonas aeruginosa in small airways (TAPAS) study in patients with cystic fibrosis: pharmacokinetics (PK)


- candidate number17507
- NTR NumberNTR4525
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR16-apr-2014
- Secondary IDsTAPAS-PK-2014 NL46747.098.13
- Public TitleTargeting antibiotics to pseudomonas aeruginosa in small airways (TAPAS) study in patients with cystic fibrosis: pharmacokinetics (PK)
- Scientific TitleTargeting antibiotics to pseudomonas aeruginosa in small airways (TAPAS) study in patients with cystic fibrosis: pharmacokinetics (PK)
- ACRONYMTAPAS-PK study in patients with CF
- hypothesisPrimary objective: To determine the safety of once daily inhalation of the recommended daily dose of tobramycin with the Akita® and the PARI-LC® Plus nebulizer in patients with CF. Systemic absorption can be used as surrogate parameter for safety. Secondary objectives: To assess tolerability of inhalation of a double dose of tobramycin by registering adverse effects (coughing, bronchospasm). To compare pharmacokinetics of the recommended dose of inhaled tobramycin once daily with either the Akita® or PARI-LC® Plus to pharmacokinetic data from the literature about standard twice daily tobramycin inhalation with the PARI-LC® Plus. Reaching a higher peak concentration by inhaling the double lung dose in one nebulisation session might be as effective, or perhaps even more effective for bacterial killing of Pseudomonas aeruginosa. Tobramycin inhalation targeted to the small airways with the Akita® nebulizer could contribute to better treatment of small airways disease in comparison with the conventional PARI-LC® Plus nebulizer. Both approaches will reduce the treatment burden and may improve adherence.
- Healt Condition(s) or Problem(s) studiedCystic Fibrosis (CF), Inhaled antibiotics, Pseudomonas aeruginosa
- Inclusion criteria Age ≥ 18 years;
 FEV1 predicted ≥ 30%;
 Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
 Chronic PA colonization;
 Ability to breathe through a mouthpiece and to use the inhaler;
 Ability to perform lung function tests;
 Written informed consent.
- Exclusion criteria Severe acute exacerbation of pulmonary infection (needing intravenous treatment);
 Patients receiving intravenous tobramycin treatment;
 Patients who are pregnant, planning to become pregnant or breastfeeding;
 Known impaired kidney function (estimated creatinine clearance < 60 ml/min);
 Known aminoglycoside hypersensitivity;
 Therapy (e.g. furosemide) or disease which may complicate evaluation of the study protocol, as judged by the investigator;
 Participation in another drug-investigating clinical study at the start or within 1 month prior to the start;
NL46747.098.13 / TAPAS-PK-2014-amendment TAPAS-PK study in patients with CF Version 3.0 February 2014 15 of 35  Inability to follow instructions of the investigator.
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlActive
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-mrt-2014
- planned closingdate31-dec-2014
- Target number of participants10
- InterventionsTen patients will be inhaling a double tobramycin dose twice at the outpatient clinic department in a cross-over setting: once with the Akita® nebulizer and the other time with the PARI-LC® Plus nebulizer.
- Primary outcomePrimary endpoint: systemic bioavailability of inhaled tobramycin, defined as serum tobramycin AUC0-24hr.
- Secondary outcome Maximum tobramycin serum level (Cmax);
 Time to maximum serum level (Tmax);
 Trough level of inhaled tobramycin (Ctrough; 24 hours post dose);
 Adverse events (coughing, bronchospasm).
- Timepoints2 study visits
- Trial web site
- status[default]
- CONTACT FOR PUBLIC QUERIES A.J. Velzen, van
- CONTACT for SCIENTIFIC QUERIES A.J. Velzen, van
- Sponsor/Initiator Erasmus Medical Center
- Funding
(Source(s) of Monetary or Material Support)
Erasmus Medical Center
- Publications
- Brief summarySmall Airways Disease (SAD) plays an important role in the pathophysiology of cystic fibrosis (CF) lung disease. Chronic infection and airway inflammation lead to progressive structural tissue damage. Chronic infection with Pseudomonas aeruginosa (Pa) causes faster progression of CF lung disease. Inhaled tobramycin has proven to be effective in delaying lung function decline in chronic Pa infections. However, SAD is not improving with current inhaled therapy, either with standard jet-nebulizer or with dry powder inhaler. The newly introduced smart nebuliser Akita® is substantially more efficient to reach the small airways. Recently, the Akita® has been shown to improve SAD when delivering dornase alpha. Hence, the use of smart nebulisers like the Akita® for tobramycin inhalation therapy in CF patients chronically infected with Pa disease might significantly reduce SAD. The bactericide efficacy of tobramycin is better with high peak levels. For intravenous use, tobramycin once daily is as effective as thrice daily and results in less toxicity. Inhaled tobramycin is dosed twice daily. Whether dosing once daily is as effective has never been studied. This would significantly reduce treatment burden. This grant application proposes a randomised study to investigate the pharmacokinetics and efficacy of inhaled tobramycin dosed once daily in patients with CF, ≥ 12 years, when using an Akita® compared with the PARI-LC® Plus. This will be conducted with a pharmacokinetic study in 10 patients to establish safety.
- Main changes (audit trail)
- RECORD16-apr-2014 - 9-mei-2014


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