1. To asses (with planar imaging) whether SPECT/CT scan are feasible in assessing pulmonary deposition of inhaled tobramycin.2. To evaluate the effect of CO2 enriched ambient air on deposition of inhaled tobramycin in bronchiectasis patients.3. To…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
o Feasibility of SPECT/CT scans
o Pulmonary deposition and pharmacokinetics
Secondary outcome
o Peak expiratory flow
o Respiratory parameters
o Borg score (subjective sensation of dyspnoea)
Background summary
Pseudomonas aeruginosa colonization is an independent predictor of mortality in
bronchiectasis patients. Tobramycin inhalation treatment is currently only
indicated for the treatment of P. aeruginosa colonization in cystic fibrosis
(CF) patients. Non-CF bronchiectasis patients often experience symptom relief
and improvement in lung function, however studies have failed to show
significant improvement. A mainly peripheral pulmonary deposition of inhaled
medication is the preferred site of choice. 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. Additionally, a nebulizer using a
breath-actuated mode, which has a flow only during inspiration in contrast to
continuous flow, could possibly also provide a better deposition. 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.
Study objective
1. To asses (with planar imaging) whether SPECT/CT scan are feasible in
assessing pulmonary deposition of inhaled tobramycin.
2. To evaluate the effect of CO2 enriched ambient air on deposition of inhaled
tobramycin in bronchiectasis patients.
3. To compare pulmonary deposition of tobramycin with the Pari LC Plus ®
nebulizer and the Aero Eclipse II ® nebulizer
Study design
Prospective randomized crossover study consisting of 3 interventions:
I) Nebulization of 99mTc-DTPA and tobramycin 150 mg without carbon dioxide
enriched air with an Aero Eclipse II ® nebulizer.
II) Nebulization of 99mTc-DTPA and tobramycin 150 mg with carbon dioxide
enriched ambient air with an Aero Eclipse II ® nebulizer.
III) Nebulization of 99mTc-DTPA and tobramycin 300 mg without carbon dioxide
enriched air with a Pari LC Plus ® nebulizer.
Phase A: SPECT/CT feasibility study with planar gamma scintigraphy (1-4
patients)
Phase B: Intervention study
After an interim analysis of the first 4 patients in phase A and B of the study
we decided to discontinue the CO2 intervention (II) as of 1-1-2015 and to limit
the number of blood collections.
Intervention
I) Nebulization of 99mTc-DTPA and tobramycin 150 mg without carbon dioxide
enriched air with an Aero Eclipse II ® nebulizer.
II) Nebulization of 99mTc-DTPA and tobramycin 150 mg with carbon dioxide
enriched ambient air with an Aero Eclipse II ® nebulizer.
III) Nebulization of 99mTc-DTPA and tobramycin 300 mg without carbon dioxide
enriched air with a Pari LC Plus ® nebulizer.
After an interim analysis of the first 4 patients in phase A and B of the study
we decided to discontinue the CO2 intervention (II) as of 1-1-2015 and to limit
the number of blood collections.
Study burden and risks
This study will consist of an inclusion visit and three study visits, all with
an intervention, nuclear imaging and pharmacokinetic assessment. Tobramycin
inhalation may cause minor discomfort due to bronchospasm but this does not
occur in patients already on tobramycin maintenance treatment. Other side
affects usually occur less frequently or only with a high intravenous dose
and/or longterm treatment (see study protocol and patient information letter).
The radiation burden is 1.25 mSv per 100 MBq. Enhanced deposition of inhaled
antibiotics could improve treatment of P. aeruginosa in bronchiectasis
patients. No direct advantages are expected in patients due to participation in
this study.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
o Bronchiectasis.
o Antibiotic inhalation therapy
Exclusion criteria
o Age <21 years.
o 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)
o Renal insufficiency defined as renal creatinine clearance of < 30 ml/minute.
o Neuromuscular diseases.
o Impaired hearing
o Pregnant or breastfeeding.
o Bronchiectasis exacerbation during last 4 weeks.
o History of panic attacks.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-001541-40-NL |
| CCMO | NL40458.029.12 |
| Other | NTR aangemeld, maar nog niet toegewezen |