In this study we want to show adequate sputum levels are obtained throughout the day after inhalation of nebulized amoxicillin clavulanic acid in hospitalized AECOPD patients.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Dose exposure data as determined by sputum concentrations of amoxicillin.
Amoxicillin levels in sputum give information on the appropriateness of the
dose given from a calculated time > MIC.
To obtain top, mid and trough sputum levels of amoxicillin between two doses,
patients are asked to give up sputum after inhalation(top), at one point during
the day(mid) and before the next inhalation (trough).
Secondary outcome
A short questionnaire is given to the patient intended to give insight in the
subjective perception of side effects after nebulization (tolerability).
Background summary
Previous research has shown that an amoxicillin concentration equal or higher
than the Minimal Inhibiting Concentration of 90% (MIC90) reduced the mean
length of hospitalization during a COPD exacerbation from 11 to 7 days.
Furthermore, most patients did not reach amoxicillin levels equal or higher
than the MIC90 when amoxicillin clavulanic acid was administered orally or
intravenously. [1,2] We hypothesize that more patients will achieve an adequate
amoxicillin level in sputum when amoxicillin clavulanic acid is administered
locally instead of systemic. Therefore, we want to apply nebulized amoxicillin
clavulanic acid by inhalation. The safety and tolerability of four escalation
single doses has been investigated in a former study in stable and hospitalized
acute exacerbations of COPD (AECOPD) patients. In this study we want to show
adequate sputum levels are obtained throughout the day after inhalation of
nebulized amoxicillin clavulanic acid in hospitalized AECOPD patients.
Study objective
In this study we want to show adequate sputum levels are obtained throughout
the day after inhalation of nebulized amoxicillin clavulanic acid in
hospitalized AECOPD patients.
Study design
The study is designed as a single-arm prospective intervention study. Patients
willing to participate in this study will follow a schedule with two times
daily inhalation of amoxicillin clavulanic acid in a fixed dose during three
days of admission (at the third day, only one inhalation takes place). At each
day of inhalation a questionnaire will be filled in to obtain insight in the
subjective perspective of side effects of inhalation (1 questionnaire per day).
After nebulization sputum samples will be collected through sputum induction.
To obtain top, mid and trough sputum levels of amoxicillin between two doses,
patients are asked to undergo sputum induction give up sputum after inhalation
(top = 30 min after nebulization), at one point during the day (mid) and before
the next inhalation (trough). Sputum induction with 3% saline is used (for all
patients in this study) since not all patients will be able to spontaneously
produce sputum at the described moments. Sputum induction will dilute the
sputum samples. This however affects mainly the top concentrations as has been
seen in other studies. For amoxicillin, effective by time > MIC, this is not
an issue since top levels are expected to be far above the MIC (as seen in
previous studies).
Intervention
The included patient will be given amoxicillin clavulanic acid by inhalation
twice daily in a concentration of 50/10 mg/ml amoxicillin clavulanic acid in
the first two days. The last day only one inhaltion takes place. Patients will
nebulize 4 ml solution of 50/10 mg/ml amoxicillin clavulanic acid (200/40 mg
amoxicillin clavulanic acid).
After the patient received the first treatment without severe adverse
reactions the treatment schedule will be two times daily. (the patient will be
questioned on this topic prior to the second nebulization) Adverse reactions
will be measured by filling in the questionnaire.
Study burden and risks
Only little is known about the risks and benefits of this product by this route
of administration. For oral or intravenous treatment several possible adverse
reactions are described in the Summary of Product Characteristics (SPC).
There is no reason to suspect other systemic adverse reactions as described in
the SPC. Additionally, local effects due to the route of administration such as
cough could occur. The patients reported no side effects in the study Stockley
et al performed with nebulization of solely amoxicillin. The STONAC 1 and 2
studies showed that patients experienced only minor side effects due to the
inhalation and was well tolerated. None of the 17 patients showed a clinical
significant reduction of FEV1 (>20%).
Potential adverse events that might occur is local irritation of the lung
tissue which could cause cough and airway narrowing as seen before in the
STONAC 1 and 2 studies and seen by other nebulized antibiotics. To prevent
airway narrowing bronchodilator therapy is given before starting the inhalation
of nebulized amoxicillin clavulanic acid. If airway narrowing occurs after
amoxicillin clavulanic acid inhalation (extra) escape medication can be used
(bronchodilators).
See IMPD for full text.
Potential Benefits: Previous research has shown that an amoxicillin
concentration in sputum higher than the MIC90 reduced the mean length of
hospitalization during a COPD exacerbation from 11 to 7 days. We hypothesize
that more patients will achieve an adequate amoxicillin level in sputum when
amoxicillin clavulanic acid is administered locally instead of systemic and
thereby exert a beneficial effect. It is unknown whether or not this effects
the clinical response.
Koningsplein 1
Enschede 7512 KZ
NL
Koningsplein 1
Enschede 7512 KZ
NL
Listed location countries
Age
Inclusion criteria
1) A clinical diagnosis of COPD, as defined by GOLD criteria
2) Hospitalized for an acute exacerbation of COPD
3) Admitted to the ward of pulmonary medicine
4) Age 40 years or over
5) Current or former smoker
Exclusion criteria
1) Current pneumonia, defined as an acute respiratory tract illness associated
with radiographic shadowing on a X-ray or CT-scan of the chest which was
neither pre-existing nor of any other cause.
2) Allergy for penicillin, amoxicillin or clavulanic acid.
3) Recently diagnosed or unresolved lung malignancy
4) amoxicillin or clavulanic acid therapy within 3 days prior to admission,
During the trial the patient cannot be treated with systemic amoxicillin or
amoxicillin clavulanic acid.
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 | EUCTR2015-005391-15-NL |
| CCMO | NL55935.044.19 |
| Other | NTR24373 |