PK and PD of Drugs for Nontuberculous Mycobacterial Diseases in Dutch Patients (NTM)

Pharmacokinetics and Pharmacodynamics of Drugs for Nontuberculous Mycobacterial Diseases in Dutch Patients

A prospective observational study in which pharmacokinetic and pharmacodynamic parameters are evaluated in a cohort of patients with NTM diseases.

Study Overview

• Status: Completed
• Conditions: Nontuberculous Mycobacterial Diseases

Detailed Description

NTM are widely distributed in the environment and can especially be found in soil and water sources. These bacteria a very similar to tuberculosis bacteria. We are not that long aware that these bacteria can cause illness. Especially in patients with a chronic lung disease are sensitive to these bacteria and are susceptible to develop an infection. A lot of ambiguity consists about the best treatment of these infections. Up till now mainly the normal treatment for tuberculosis is used, however, the time period during which these medicines should be used and what dose should be used is mainly unknown.

To investigate whether the dose used at this moment is right a pharmacokinetic curve will be taken at steady-state.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Centre Groningen
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboud University Medical Centre Nijmegen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with NTM infection are generally middle aged or higher aged, white males with COPD or bronchiectasis. They will be recruited from the outpatient clinics of University Centre for Chronic Diseases Dekkerswald, Tuberculosis Centre Beatrixoord or other outpatient clinics in The Netherlands. Both newly diagnosed and already treated patients with NTM disease will be recruited.

Description

Inclusion Criteria:

• currently treated for NTM infection or recently diagnosed with NTM infection starting treatment at University Centre for Chronic Diseases Dekkerswald (Groesbeek), Centre for Revalidation Beatrixoord (Haren), or other outpatient clinics in The Netherlands.
• Diagnosis and treatment according to American Thoracic Society (ATS) criteria for NTM infections. Patients with pulmonary NTM infections (possible with extrapulmonary localizations as well) are eligible
• Treated with at least rifampicin and ethambutol and optionally with isoniazid, clarithromycin or azithromycin on a daily basis
• Age at least 18 years
• Patient has been using drugs for at least two weeks when steady state concentrations of the used drugs are expected
• Informed consent has been signed

Exclusion Criteria:

• The medical state of the patients does not allow inclusion according to the physician in attendance.
• The patients' clinical parameters urge immediate cessation of drugs.
• The patient is pregnant.
• Significant hepatic or renal dysfunction based on chemistry parameters (grade 1 according to an international adverse event grading system, see http:/ctep.cancer.gov) or symptomatic liver dysfunction (nausea and vomiting).
• Patients with cystic fibrosis, since these show deviating pharmacokinetics for many drugs.
• Patients with HIV infection, since these may show deviating pharmacokinetics for the drugs used in NTM disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NTM infection; Patients with NTM infection are generally middle aged or higher aged, white males with COPD or bronchiectasis. They will be recruited from the outpatient clinics of University Centre for Chronic Diseases Dekkerswald, Tuberculosis Centre Beatrixoord or other outpatient clinics in The Netherlands. Both newly diagnosed and already treated patients with NTM disease will be recruited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters of antimycobacterial drugs in NTM treatment	after at least 2 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Determinants of pharmacokinetic parameters	after at least 2 weeks of treatment
Assessment of MIC values and pharmacodynamic parameters for response	once a month starting after two weeks of treatment;last assessment at 6 months
Association of pharmacokinetic and pharmacodynamic parameters with treatment outcome and toxicity	entire study

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Rob Aarnoutse, Pharm D PhD, Radboud University Medical Center; Principal Investigator: Jan- Willem Alffenaar, PharmD PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: January 18, 2010
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (Estimate): January 20, 2010

Study Record Updates

• Last Update Posted (Estimate): May 22, 2012
• Last Update Submitted That Met QC Criteria: May 21, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; Nontuberculous mycobacterial diseases
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections
• Other Study ID Numbers: NL29420.091.09