The first main objective is to investigate the pharmacokinetic properties of dry powder amikacin at different dosages and compare the peak serum values to a single i.v. dose. The secondary main objective is to assess the local tolerability of dry…
ID
Source
Brief title
Condition
- Mycobacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following pharmacokinetic parameters will be calculated: actual dose (dose
minus remainder in inhaler after inhalation), AUC0-24 (area under the curve
from 0-24 h), Cmax (maximum serum concentration), Tmax (time to maximum serum
concentration).
For local tolerability of the inhalation of dry powder amikacin the following
procedures will be done. Both points need to have a positive result.
* Drop of FEV1 of >15 % (lung function measurement)
* Questioning/ registration adverse events
Secondary outcome
Inspiratory parameters during the inhalation maneuver. Following parameters
will be calculated:
* dPmax (maximum pressure drop)
* Vi (inhaled volume)
* Ti (total inhalation time)
* PIF (peak inspiratory flow rate)
* MIF (mean inspiratory flow rate)
* FIR (average flow increase rate between 20% and 80% of PIF)
Background summary
Multidrug-resistant tuberculosis (MDR-TB) is defined as tuberculosis resistant
to isoniazid and rifampicin. The incidence of MDR-TB worldwide is 3.9% for new
cases and 21% for previously treated cases. However, the incidence of
previously treated cases can rise to above 50% in eastern European
countries.[1] With increasing frequency of MDR-TB (and even extensively
drug-resistant types), morbidity and mortality due to TB fail to decline
worldwide. Cornerstones of MDR-TB treatment are aminoglycosides, like amikacin,
and fluoroquinolones. Amikacin is given intravenously for 6-8 months in the
usual MDR-TB treatment. Since 2016 it can also be given for 4-6 months in the
short-course treatment for MDR-TB. In many countries, this implicates long
hospital admissions for the patients, as well as problems in venous access,
often necessitating surgical insertion of venous access ports. Amikacin has the
most potent effect when reaching a high peak serum concentration and this means
that high doses have to be administered. Treatment with amikacin by inhalation
would be a tremendous advantage due to the high local dose in the lungs,
obtaining high local levels without the possible toxicity due to high serum
levels.
Study objective
The first main objective is to investigate the pharmacokinetic properties of
dry powder amikacin at different dosages and compare the peak serum values to a
single i.v. dose.
The secondary main objective is to assess the local tolerability of dry powder
amikacin via the Cyclops* at different dosages.
Study design
single center, active control, ascending dose response study
Study burden and risks
All participants included in this study are patients with DSTB, who are
admitted at the Tuberculosis Center Beatrixoord. They will receive 3 different
doses of amikacin using the DPI with (at least) one week in between doses, they
will also receive one dose of intravenous amikacin. Before using the dry powder
inhaler (DPI) they will receive instructions and their inspiratory flow will be
tested. Before each test dose an indwelling canula will be inserted and before
and after each test dose in total 9 blood samples will be collected. To
investigate local tolerability, lung function tests will be performed and the
occurrence of adverse events will be scored.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
* Age above 18 years
* Diagnosed with DSTB, either by culture or molecular testing
* Obtained written informed consent
Exclusion criteria
* Pregnancy or breast feeding
* Subjects with known or suspected (by spontaneous reporting or by active
questioning) renal, auditory, vestibular or neuromuscular dysfunction.
* History of adverse events on previous amikacin or other aminoglycoside use
(by spontaneous reporting nor by active questioning)
* Concurrent use of aminoglycosides, cyclosporin, cisplatin, amfotericin B,
cephalosporins, polymyxins and vancomycin
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 | EUCTR2018-001893-95-NL |
| CCMO | NL66924.042.18 |