PK/PD of Ertapenem In Patients With TB

Study Overview
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Brief Summary
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Rationale: 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. Objective: The main objective of this prospective clinical trial is to evaluate pharmacokinetics of a standard dose (2000mg) of ertapenem in TB patients. This clinical trial will provide important information on PK of ertapenem in TB patients for future studies. Data can be used for limited sampling strategies for ertapenem based on a pharmacokinetic population model constructed from the full PK curves of the patients. Study design: A prospective pharmacokinetic study. Study population: 12 TB patients. Intervention: Single dose of 2000mg in a 30 minutes intravenous infusion. Main study parameters/endpoints: The pharmacokinetic parameters (Vd, Cl, AUC, etc) of ertapenem are the primary endpoints of the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most likely the best predictive parameters for efficacy of ertapenem treatment and will be calculated for a range of M tuberculosis isolates.

Official Title
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Pharmacokinetics and Pharmacodynamics of Ertapenem in Patients With Tuberculosis

Conditions
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PK of Ertapenem in TB Patients

Intervention / Treatment
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* Drug: ertapenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture and / or molecular test Adults: from 18 years until 64 years of age Exclusion Criteria: -Contra-indications for ertapenem: There are few adverse effects of ertapenem. The only absolute contra- indication is a previous anaphylactic reaction to ertapenem or other β-lactam antibiotic. Renal Insufficiency, defined by a eGFR of 30ml/min Pregnancy HIV Body weight < 40 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ertapenem<br>single dose ertapenem | Drug: ertapenem<br>* single dose of 2000mg ertapenem IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | main objective of this prospective clinical trial is to evaluate AUC of a standard dose (1000mg) of ertapenem in TB patients | first day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: number of patients with organ dysfunction | renal function(eGFR) and liver enzymes(ALAT; ASAT) | day 1 and day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ertapenem, tuberculosis, pharmacokinetics