To investigate whether inhalation of nebulised amoxicillin clavulanic acid is effective in reaching amoxicillin sputum levels >= MIC 90 in patient with an exacerbation of COPD.
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary: At day 3 sputum samples will be collected and the amoxicillin
concentration will be determined in order to obtain a number (percentage) of
patients that adhere to an amoxicillin sputum level higher than the MIC90.
Secondary outcome
Secondary:
• To investigate whether nebulisation of amoxicillin clavulanic acid results in
a decrease of hospitalisation days of patients with an exacerbation of COPD
compared to the ASPECT study.
• To investigate the tolerability of nebulised amoxicillin clavulanic acid.
• To obtain information on distribution and systemic exposure of amoxicillin
when nebulised.
Background summary
Previous research has shown that an amoxicillin concentration higher than the
Minimal Inhibiting Concentration of 90% (MIC90) reduced the mean length of
hospitalisation during a COPD exacerbation from 11 to 7 days. Furthermore
most patients did not reach amoxicillin levels equal or higher than the Minimal
Inhibiting Concentration of 90% (MIC90) when amoxicillin clavulanic acid was
administered orally or intravenously. We think that more patients will achieve
an adequate amoxicillin level in sputum when amoxicillin clavulanic acid is
administered locally instead of systemic. Therefore in this study we want to
apply nebulised amoxicillin clavulanic acid by inhalation.
Study objective
To investigate whether inhalation of nebulised amoxicillin clavulanic acid is
effective in reaching amoxicillin sputum levels >= MIC 90 in patient with an
exacerbation of COPD.
Study design
The study is designed as a single-arm prospective intervention study
Intervention
Patients that are considered for treatment with amoxicillin clavulanic acid
will receive treatment by inhalation of 25/5 mg nebulised amoxicillin
clavulanic acid twice daily instead of oral or intravenously administered
amoxicillin. Further treatment will be according to common daily practice
Study burden and risks
Risk: Aerosolized delivery of antimicrobial agents is an attractive option for
management of pulmonary infections, as this is an ideal method of providing
high local drug concentrations while minimizing systemic exposure. Inhalation
of nebulised amoxicillin clavulanic acid has not been described in literature.
There are only two studies on tolerability of inhalation of amoxicillin. In
these studies amoxicillin was well tolerated. However their sample sizes were
small. There are no signs to suspect tolerability issues no more then there are
with systemic administration. Local adverse effects such as cough, wheezing,
shortness of breath, and respiratory irritation can occur with aerosolized
delivery of antimicrobials. Therefore security measures will be taken. Benefit:
This treatment has the potential of achieving better results, i.e. shortening
of exacerbation than oral or intravenous administration. When the hypothesis is
correct that failure of treatment by oral or intravenous intake results is
related to low sputum levels then this new way of local administration could be
off a substantial benefit in the treatment of exacerbations of COPD.
Haaksbergerstraat 55
7513 ER Enschede
Nederland
Haaksbergerstraat 55
7513 ER Enschede
Nederland
Listed location countries
Age
Inclusion criteria
• A clinical diagnosis of COPD, as defined by GOLD criteria,
• Admitted with signs and symptoms of an exacerbation of COPD, defined as an acute negative change from the baseline, reported by the patient, in dyspnoea and/or sputum volume and/or colour of sputum (yellowish or greenish sputum) and/or cough
• Age 40 years or over
• Current or former smoker.
Exclusion criteria
• Impaired renal function (GFR < 30)
• Current pneumonia, defined as an acute respiratory tract illness associated with radiographic shadowing on a chest radiograph which was neither pre-existing nor of any other cause.
• Allergy for penicillin, amoxicillin or clavulanic acid
• Respiratory insuffiency and hypercapnia measured by arterial blood gas analyses
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 | EUCTR2011-001972-20-NL |
| CCMO | NL35340.044.11 |
| Other | NTR nummer volgt |