|- candidate number||12289|
|- NTR Number||NTR3407|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||24-apr-2012|
|- Secondary IDs||Pro12/15 CWO|
|- Public Title||Effect Of CO2 On Nebulized Tobramycin.|
|- Scientific Title||Effect of Carbon Dioxide Enriched Ambient Air on Pharmacokinetics and Deposition In Bronchiectasis Patients Using Tobramycin Inhalation: A proof of concept study.|
|- hypothesis||1. Evaluation of pulmonary deposition of inhaled Tobramycin with 99mTc-DTPA tracer is feasible using SPECT-CT scans;|
2a. Pulmonary deposition of Tobramycin improves with concomitant inhalation of carbon dioxide enriched ambient air;
2b. Pulmonary deposition of Tobramycin with the breath-actuated mode of the AeroEclipse II nebulizer and adjusted dose is equal to deposition with the Pari LC plus nebulizer.
|- Healt Condition(s) or Problem(s) studied||Bronchiectasis|
|- Inclusion criteria||1. Bronchiectasis;|
2. Antibiotic inhalation therapy.
|- Exclusion criteria||1. Age <21 years;|
2. Chronic respiratory insufficiency defined according to the GOLD criteria (PaO2 < 60 mmHg or PaCO2 > 50 mmHg, WHO Global Initiative for Chronic Obstructive Lung Disease 2006);
3. Renal insufficiency defined as renal creatinine clearance of < 30 ml/minute;
4. Neuromuscular diseases;
5. Impaired hearing;
6. Pregnant or breastfeeding;
7. Bronchiectasis exacerbation during last 4 weeks;
8. History of panic attacks.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jun-2012|
|- planned closingdate||1-dec-2013|
|- Target number of participants||14|
|- Interventions||1. Nebulization of 99mTc-DTPA and tobramycin 125 mg without carbon dioxide enriched air with an Aero Eclipse II ® nebulizer;|
2. Nebulization of 99mTc-DTPA and tobramycin 125 mg with carbon dioxide enriched ambient air with an Aero Eclipse II ® nebulizer;
3. Nebulization of 99mTc-DTPA and tobramycin 300 mg without carbon dioxide enriched air with a Pari LC Plus ® nebulizer.
The interventions have a duration of 3 days with at least 72 hours in between and a maximum pause of 1 week.
|- Primary outcome||Phase A study:|
Feasibility study (SPECT/CT). Mean clearance rate (and range) of 99mTc-DTPA.
Phase B study:
1. Total and peripheral deposition of inhaled tobramycin (with and without carbon dioxide and with two different nebulizers);
2. Pharmacokinetics: C max (peak concentration), AUC (0-8 hours), T max (time to reach maximum concentration), T1/2 (half life).
|- Secondary outcome||1. Peak expiratory flow;|
2. Respiratory parameters;
3. Borg score (subjective sensation of dyspnoea).
|- Timepoints||Analysis at end of study.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||MD. T. Paff|
|- CONTACT for SCIENTIFIC QUERIES||MD. T. Paff|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center, Teva Pharma Netherlands BV|
|- Brief summary||Pseudomonas aeruginosa colonization is an independent predictor of mortality in bronchiectasis patients. Non-CF bronchiectasis patients often experience symptom relief and improvement in lung function, however studies have failed to show significant improvement. Enhancing deposition of inhaled antibiotics and lung recruitment may improve the response to inhaled antibiotic treatment. Inhaling a low concentration of carbon dioxide (CO2) during antibiotic nebulization alters respiratory parameters. By changing these parameters one can try to alter the peripheral deposition of inhaled medication, which may improve treatment. SPECT/CT is the preferred technique to obtain information on deposition of inhaled drugs. However it is unknown if these measurements are feasible with inhalation of technetium DTPA (99mTc-DTPA) and tobramycin, due to the requirement of a relatively steady state uptake. This randomised cross-over proof of principle study investigates the feasibility of SPECT-CT scans in the evaluation of pulmonary deposition of Tobramycin. In addition, concomitant inhalation of CO2 enriched ambient air and the use of the breath-actuated mode of the AeroEclipse II nebulizer with adjusted Tobramycin dose are evaluated. |
|- Main changes (audit trail)|
|- RECORD||24-apr-2012 - 28-aug-2012|