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Completed

NCT Number: NCT01832987

Pharmacokinetic Parameters of Co-trimoxazole

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with dried blood spot (DBS) analysis, the exposure to co-trimoxazole could be analyzed with only some blood drops withdrawn with a finger prick on paper.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 Furthermore, the analysis of dried blood spots will be clinically validated by comparing results of blood samples withdrawn from venous blood versus withdrawn by finger prick and transferred to filter paper.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.

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Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

UMCG - Tuberculosis Center

Groningen, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • TB Patients with normal susceptible Mycobacterium tuberculosis
  • Patients older than 17 and younger than 64 years.

Exclusion criteria

  • Pregnancy or breast feeding
  • Patients with hypersensitivity to sulfonamide or trimethoprim
  • Concomitant treatment with vitamin K antagonists (acenocoumarol)
  • Patients with preexisting renal dysfunction or concomitant treatment of angiotensin converting enzyme inhibitors and potassium -sparing diuretics) that may exacerbate the hyperkalemic effect of SXT.
  • Patients treated with methotrexate, phenytoin, sulfonylureas (glibenclamide, gliclazide, glimepiride en tolbutamide) or procainamide hydrochloride.
  • Patients that have gastrointestinal complaints like diarrhea and vomiting (observed)
  • Patients that have experienced an adverse effect to SXT or similar antibiotic drugs.
  • Patients with HIV or AIDS.

Treatment and study plan

co-trimoxazole

Drug

On 4, 5 or 6 consecutive days, co-trimoxazole 960 mg will be added to the normal treatment regimen

Other names: Sulfamethoxazole/trimethoprim

Primary outcomes

  1. AUC

    Time frame: 4th, 5th or 6th day

    Measuring the AUC over 24 hours of sulfamethoxazole, one out of two compounds of co-trimoxazole after obtaining steady state (960 mg co-trimoxazole).

Secondary outcomes

  1. Determination of the AUC/MIC and T>MIC

    Time frame: 4th, 5th or 6th day

    Determination of the area under the curve divided by the mean inhibitory concentration and the time above MIC.

  2. Validating DBS analysis

    Time frame: 4th, 5th or 6th day

    Validating the analysis of dried blood spots for therapeutic drug monitoring by comparing the concentration measured in venous blood with the concentration measured using the dried blood spot method.

Other outcomes

  1. Population pharmacokinetic model and limited sampling strategies

    Time frame: 4th, 5th or 6th day

    Developing a population pharmacokinetic model to predict pharmacokinetic parameters of sulfamethoxazole. With this population pharmacokinetic model, a limited sampling strategy will be developed.

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Registry information

Official study title

Pharmacokinetic Parameters of 960 mg Co-trimoxazole Once Daily in Patients With Tuberculosis

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Apr 16, 2013
Registry last updated
Sep 16, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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