Clinical trial NCT01730664: PK/PD of Ertapenem In Patients With TB
Official title: Pharmacokinetics and Pharmacodynamics of Ertapenem in Patients With Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: PK of Ertapenem in TB Patients
Keywords: ertapenem
tuberculosis
pharmacokinetics
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2012-11-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: AUC
timeFrame: first day
Secondary outcomes:
measure: Safety: number of patients with organ dysfunction
timeFrame: day 1 and day 3
Other outcomes:
measure: limited sampling strategies
timeFrame: day 1
Locations:
city: Groningen
country: Netherlands
facility: UMCG - Tuberculosis Center
Study officials:
References:
citation: Tremblay LW, Fan F, Blanchard JS. Biochemical and structural characterization of Mycobacterium tuberculosis beta-lactamase with the carbapenems ertapenem and doripenem. Biochemistry. 2010 May 4;49(17):3766-73. doi: 10.1021/bi100232q.