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Personalization of AntiTB Treatment: Evaluation of Pharmacological Determinants of Treatment Response (PAT)

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ClinicalTrials.gov Identifier: NCT03416309
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
Research Center Borstel
Information provided by (Responsible Party):
Ilaria Motta, University of Turin, Italy

Brief Summary:
The aim of the study is to investigate the possible correlation of plasma drug concentrations with Time To Positivity (TTP) in liquid culture in patients with active pulmonary multi sensitive TB in the first two weeks of treatment. Secondary aims are: the correlation between plasma drug concentrations and hepato/neuro toxicity; the impact of different allelic variants on PK data, toxicity and TTP in liquid culture; the feasibility of using dried blood/plasma spots to measure plasma concentrations of anti-TB drugs and determine genetic polymorphisms.

Condition or disease
Tuberculosis, Pulmonary

  Show Detailed Description

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 257 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 6 Months
Official Title: Personalization of AntiTB Treatment: Evaluation of Pharmacological Determinants of Treatment Response
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Correlation between AUC of RHZE and TTP [ Time Frame: 1 week from start of treatment ]
    Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the first week of treatment.

  2. Correlation between AUC of RHZE and TTP [ Time Frame: 2 weeks from start of treatment ]
    Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with the change in Time To Positivity (TTP) in liquid culture in patients with active pulmonary TB between the baseline and the second week of treatment.


Secondary Outcome Measures :
  1. Correlation between AUC of RHZE and toxicity [ Time Frame: 1 week and 2 weeks from start of treatment ]
    Investigate the correlation of plasma drug concentrations (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, HRZE) with hepatotoxicity (increase of AST and/or ALT) and neurotoxicity (peripheral neuropathy)

  2. Correlation between PG and AUC of RHZE [ Time Frame: 1 week and 2 weeks from start of treatment ]
    Investigate the impact of different allelic variants of NAT2, SLCO1B1, ABCB1, VDR on AUC of RHZE toxicity and TTP in liquid culture

  3. Assess the consistency of results using of DPS for measuring the plasma drug concentrations [ Time Frame: 1 week and 2 weeks from start of treatment ]
    Assess the consistency of using dried plasma spots to measure plasma concentrations of anti-TB drugs comparing to plasma samples

  4. Correlate AUC of RHZE with antiTB response [ Time Frame: 6 months after end of treatment ]
    A pharmacometric model will be develop to correlate pharmacokinetics (AUC of RHZE) with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.

  5. Correlate PG with antiTB response [ Time Frame: 6 months after end of treatment ]
    A pharmacometric model will be develop to correlate PG with the anti-TB treatment response (clinical and TTP) of the standard first-line anti-TB regimen.


Biospecimen Retention:   Samples With DNA
DNA samples will be stored in an appropriate place recognizable by inscriptions or encodings that will in any way be attributable to any personal or sensitive data of the patient in full respect of privacy, and will be accessible only by the staff involved in the study in full compliance with the safety standards.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients diagnosed with pulmonary TB referred from other primary health centers All the patients with diagnosis of pulmonary DS (drug sensitive) TB will be enrolled.

The patients will received standard antitubercular drugs according to international guidelines (RIF 10 mg/kg, INH 5 mg/kg maximum dose 300 mg, ETB 15-20 mg/kg, PZA 25 mg/kg maximum dose 2000 mg) in fasten condition, once daily.

Criteria

Inclusion Criteria:

  • signed informed consent
  • age >=18 years;
  • pulmonary tuberculosis defined by positive sputum microscopy (waiting for culture confirmation)
  • sensitivity to first-line anti-TB drugs;
  • normal liver and renal function.

Exclusion Criteria:

  • severe malnutrition;
  • HIV infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416309


Contacts
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Contact: Ilaria Motta +390114393856 ilaria.motta@unito.it
Contact: Andrea Calcagno +390114393856 andrea.calcagno@unito.it

Locations
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Italy
Ospedale Amedeo di Savoia Recruiting
Torino, Italy, 10149
Contact: Ilaria Motta, MD    +390114393956    ilaria.motta@unito.it   
Contact: Andrea Calcagno, MD    +390114393856    andrea.calcagno@unito.it   
Sponsors and Collaborators
University of Turin, Italy
Research Center Borstel
Investigators
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Principal Investigator: Ilaria Motta, MD University of Turin, Italy

Additional Information:

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Responsible Party: Ilaria Motta, Principal Investigator, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT03416309     History of Changes
Other Study ID Numbers: PAT_Study
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We can share anonymous data upon request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ilaria Motta, University of Turin, Italy:
pharmacokinetics
pharmacogenetics
Time To Positivity
Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections