The main objective is to evaluate pharmacokinetics of a maximum standard dose (2000mg) of ertapenem in TB patients.
ID
Source
Brief title
Condition
- Mycobacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main objective of this prospective clinical trial is to characterise the
pharmacokinetics of ertapenem in tuberculosis patients.
Secondary outcome
To evaluate T>MIC and AUC/MIC ratio
To evaluate limited sampling strategies based on a pharmacokinetic population
model to predict ertapenem AUC0-24h
To evaluate alternative blood sampling
Background summary
Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB)
is a real challenge as failure in response to treatment and serious
side-effects are frequently encountered. New, more effective drugs with less
side effects are therefore urgently needed to solve this problem. Although
several new drugs against TB are in the pipeline, physicians currently have
limited treatment options for treatment of complicated MDR/XDR-TB cases.
Therefore, drugs developed and labeled for other infectious diseases are
evaluated for TB.
Study objective
The main objective is to evaluate pharmacokinetics of a maximum standard dose
(2000mg) of ertapenem in TB patients.
Study design
In a prospective clinical trial the pharmacokinetic parameters of ertapenem
will be evaluated.
This study is an pharmacokinetic study to characterise the pharmacokinetics of
a single dose of ertapenem. Plasma samples (2 ml) will be taken at t= 0, 0.5,
1, 2, 3, 4, 8, 12, 24 hr post dosage. Also dried blood spot and mitra tip
samples will be taken by fingerprick at timepoints 1 (peak), 4 (middle) and 12
(through) hr post dosage. MIC values for ertapenem will be determined if the
specimen is cultured. The drug susceptibility test of the available M.
tuberculosis isolates are performed with the Middlebrook 7H10 agar dilution
method. The area under the concentration-time curve up to 24 hours post dosage
(AUC0-24h) for plasma will be determined with a standard one-compartmental
pharmacokinetic method using KINFIT module of MW Pharm 3.60 (Mediware, The
Netherlands). To assure safety of the patients that will participate in the
study the patients will be screened for a history of hypersensitivity or
allergic reactions for carbapenems or *-lactam antibiotics (like penicillins
and cephalosporins). As ertapenem is excreted primarily (80%) by the kidneys,
renal function will be examined. Laboratory tests (clinical chemistry,
urinalysis; including electrolytes (K, Mg, Na, Ca), transaminase values, serum
creatinine and bilirubin) will be evaluated the day before the study drug is
administered as part of routine treatment. During and after administration of
ertapenem a physician will be available in the presence of the patient.
Study burden and risks
The risks of the use of ertapenem for patients are low, so far side effects
occur in a low percentage and if present are of minor importance.
The patients may experience some minor discomfort due to the PK-sampling
performed using an indwelling iv catheter. There is no benefit for the
individual patient. Future patients with drug resistent tuberculosis (MDR-tb:
multidrug resistant tuberculosis and XDR-tb: extensively drug resistant
tuberculosis) may benefit from this study.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Patients with tuberculosis, caused by Mycobacterium tuberculosis or by M. africanum
- Adults: from 18 until 64 years of age
Exclusion criteria
o There are few adverse effects of ertapenem. The only absolute contra-indication is a previous anaphylactic reaction to ertapenem or other *-lactam antibiotic.
o Renal Insufficiency, defined by a eGFR of 30ml/min
o Pregnancy
o HIV
o Body weight < 40 kg
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 | EUCTR2012-003386-18-NL |
| ClinicalTrials.gov | NCT01730664 |
| CCMO | NL41380.042.12 |