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Salivary Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs

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ClinicalTrials.gov Identifier: NCT03080012
Recruitment Status : Completed
First Posted : March 15, 2017
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Jan-Willem C Alffenaar, University Medical Center Groningen

Tracking Information
First Submitted Date February 9, 2017
First Posted Date March 15, 2017
Last Update Posted Date November 21, 2018
Actual Study Start Date March 7, 2017
Actual Primary Completion Date May 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 8, 2017)
Saliva-plasma ratio or saliva-serum ratio [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
Ratio of salivary versus blood concentration calculated with salivary and plasma/serum values of area under the time-concentration curve (AUC)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 8, 2017)
  • Salivary drug concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Measured drug concentration in saliva
  • Plasma/serum drug concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Measured drug concentration in plasma or serum
  • Area under the time-concentration curve (AUC) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Peak concentration (Cmax) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Time of peak concentration (Tmax) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Trough concentration (Cmin) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Clearance (Cl) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Half-life (t1/2) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
  • Elimination constant (Kel) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Salivary Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs
Official Title An Observational Study of Salivary Versus Blood Concentrations of Various Anti-Tuberculosis Drugs in Tuberculosis Patients
Brief Summary In tuberculosis patients, salivary concentrations will be compared to plasma/serum concentrations of several anti-tuberculosis drugs. If salivary concentrations correctly represent blood concentrations, this non-invasive sampling of saliva could be used for TDM of the tested drugs.
Detailed Description

TDM (Therapeutic Drug Monitoring) with blood samples is already part of the treatment of some tuberculosis (TB) patients to reduce development of drug resistance and toxic drug concentrations. Performing TDM with saliva instead of plasma or serum could reduce the burden of blood sampling. This study examines if this non-invasive sampling of saliva could be used for TDM of several anti-TB drugs.

The study is an observational cohort study with adult tuberculosis patients as subjects. The drugs that are studied are isoniazid, rifampicin, ethambutol, pyrazinamide, moxifloxacin, amikacin, kanamycin, capreomycin, ethionamide, prothionamide, cycloserine, terizidone, linezolid, clofazimine, bedaquiline, delamanid, p-aminosalicylic acid (PAS), imipenem-cilastatin, meropenem, ertapenem, amoxicillin-clavulanate and thioacetazone.

Saliva samples will be taken simultaneously with blood samples for standard TDM. Serum/plasma and saliva drug concentrations will be determined with a validated LC-MS/MS (liquid chromatography-tandem mass spectrometry) method. The correlation and linearity between saliva and plasma/serum concentrations will be tested. The saliva-plasma or serum ratio based on area under the time-concentration curve (AUC) is calculated for the investigated anti-TB drugs. Also pharmacokinetic parameters in serum/plasma and saliva will be calculated and compared to provide a complete image of pharmacokinetics of the anti-TB drugs in saliva.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Tuberculosis patients of University Medical Center Groningen Beatrixoord, Haren, The Netherlands.
Condition Tuberculosis
Intervention
  • Other: Saliva sampling
    Stimulated saliva samples are taken using cotton rolls.
  • Other: Plasma/serum sampling
    Simultaneously with saliva sampling.
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: November 20, 2018)
24
Original Estimated Enrollment
 (submitted: March 8, 2017)
25
Actual Study Completion Date May 2, 2018
Actual Primary Completion Date May 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Tuberculosis is confirmed by culture or molecular test
  • Patient is treated with anti-tuberculosis drugs included in study
  • Patient receives Therapeutic Drug Monitoring (TDM) in routine care
  • Patient signed informed consent

Exclusion Criteria:

  • Patient with severe problems in the oral cavity, making saliva sampling painful
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT03080012
Other Study ID Numbers SALIV-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: Encoded data can be shared for scientific use up to 15 years after study completion.
Responsible Party Jan-Willem C Alffenaar, University Medical Center Groningen
Study Sponsor University Medical Center Groningen
Collaborators Not Provided
Investigators
Principal Investigator: Jan-Willem Alffenaar, PhD, PharmD University Medical Center Groningen
PRS Account University Medical Center Groningen
Verification Date November 2018