Pharmacokinetic Parameters of Co-trimoxazole
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 2

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.
      Co-trimoxazole consists of sulfamethoxazole and trimethoprim. Sulfamethoxazole could be
      effective in the treatment of tuberculosis as shown by Forgacs et al. and Huang et al.

      Furthermore, with dried blood spot (DBS) analysis, the exposure to co-trimoxazole could be
      analyzed with only some blood drops withdrawn with a finger prick on paper. This paper is
      suitable for storage, transportation and subsequently analysis without additional cooling or
      storage requirements.

      Objective:

      The main objective of this prospective clinical trial is to evaluate pharmacokinetics of 960
      mg co-trimoxazole in TB patients. This clinical trial will provide important information on
      PK of co-trimoxazole in TB patients for future studies.

      The second objective is to calculate the T>MIC and AUC0-24h/Minimal inhibitory concentration
      (MIC) ratio as efficacy predicting parameter. Furthermore, the analysis of dried blood spots
      will be clinically validated by comparing results of blood samples withdrawn from venous
      blood versus withdrawn by finger prick and transferred to filter paper. Retrospectively, data
      from this study can be used for limited sampling strategies for co-trimoxazole 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: on 4 to 6 days, 960 mg co-trimoxazole daily will be added to the normal
      treatment regimen.

      Main study parameters/endpoints:

      The pharmacokinetic parameters (Vd, Cl, AUC, etc) of co-trimoxazole 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 co-trimoxazole treatment and will be
      calculated for a range of M tuberculosis isolates.
    


Intervention name(s): co-trimoxazole
Intervention type(s): Drug
Intervention description(s): On 4, 5 or 6 consecutive days, co-trimoxazole 960 mg will be added to the normal treatment regimen
Other intervention name(s): Sulfamethoxazole/trimethoprim
Intervention MeSH terms: Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Sulfamethoxazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: co-trimoxazole; sulfamethoxazole; tuberculosis; pharmacokinetics