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Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes (SOUTH)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Makerere University
Sponsor:
Information provided by (Responsible Party):
Infectious Diseases Institute, Makerere University
ClinicalTrials.gov Identifier:
NCT01782950
First received: January 9, 2013
Last updated: February 1, 2013
Last verified: January 2013

January 9, 2013
February 1, 2013
February 2013
March 2016   (final data collection date for primary outcome measure)
clinical outcome [ Time Frame: At the end of treatment (6 months after enrolmet) ] [ Designated as safety issue: No ]
To investigate the association between serum concentrations of antituberculosis drugs and tuberculosis treatment response in HIV-TB-co-infected individuals.
Same as current
Complete list of historical versions of study NCT01782950 on ClinicalTrials.gov Archive Site
  • Cmax [ Time Frame: At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation ] [ Designated as safety issue: No ]
    To investigate the steady-state pharmacokinetic parameters of anti-TB drugs at different time-points over the course of TB-treatment
  • Number of adverse events [ Time Frame: 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of anti-TB drugs based on the WHO guidelines
  • ART trough levels [ Time Frame: At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation ] [ Designated as safety issue: No ]
    To correlate the effect of anti-TB drugs on plasma concentrations of efavirenz or protease inhibitors and vice versa.
  • Isoniazid Cmax [ Time Frame: At 2 weeks, 8 weeks and 24 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the effect of acetylator geno-and phenotype (NAT-2 gene) on isoniazid plasma concentrations and toxicity
Same as current
Not Provided
Not Provided
 
Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes
Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes in HIV-tuberculosis Co-infected Ugandan Adults

Tuberculosis (TB) is a leading cause of death in HIV-infected individuals. There are insufficient data correlating concentrations of anti-TB drugs with treatment response. We hypothesize that sub-therapeutic concentrations of anti-TB drugs are associated with inadequate TB treatment response to Mycobacterium tuberculosis.

During the study periodic monitoring will be conducted to ensure that the protocol and Good Clinical Practices (GCPs) are being followed.The monitors may review source documents to confirm that the data recorded on CRFs is accurate. The study site may be subject to review by the Institutional Review Board (IRB) and/or appropriate regulatory authorities.

A CRF will be completed for each included subject and will be signed by the investigator or by an authorized staff member to attest that the data is true. Any corrections to entries made in the CRFs, source documents must be dated, initialed and explained (if necessary) and should not obscure the original entry. Qualit assurance will as also be performed regularly on the CRFs.

The primary end point will be analyzed using Time to event (cure, death, relapse etc)analysis and failure rates and hazard ratios will be calculated accordig to categorical drug concentrations with proposed cutt offs.

Secondary end points will be analysed using time to event for occurence of toxicities which will also be corelated to the drug concentrations.

Interventional
Phase 4
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
AIDS With Tuberculosis
Drug: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide
Rifampicin, Isoniazid, Ethambutol, Pyrazinamide: 3, 4 or 5 tablets daily for weight below 55kg, above 55kg or above 70kg respectively for first 2 months followed by Rifampicin, Isoniazid: 3, 4 or 5 tablets daily for patients' weight below 55kg, above 55kg or above 70kg respectively for 4 months
Other Names:
  • Forecox Trac
  • and Montozid
anti-tuberculosis drugs
Rifampicin, Isoniazid, Ethambutol, Pyrazinamide tablets 3 to 5 tablets once daily for 2 months followed by Rifampicin, Isoniazid 3 to 5 tablets once daily for 4 months
Intervention: Drug: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
400
March 2016
March 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Evidence of a personally signed and dated informed consent
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Age of ≥18 years
  • First episode of pulmonary TB i.e. proven or highly suspected TB considered for TB treatment qualifying for 6 months anti-Tb drugs regimen
  • Confirmed HIV-1 infection

Exclusion Criteria:

  • Unable to provide informed consent
  • Documented or highly suspected TB infection of any organs/systems other than the lung requiring TB treatment longer than 6 months
  • Previously treated for a mycobacterial infection (TB or atypical mycobacterial infection, active or latent)
  • Pregnancy or planned pregnancy within the next year
  • Unwillingness to perform pregnancy test
  • Decompensated liver disease and/or aminotransferases >5x ULN
  • GFR < 50 ml/min
  • Co-morbidities reducing life expectancy to <1 year (e.g. cancer)
  • Patient wishes to take part in another interventional study
Both
18 Years and older
No
Contact: Andrew Kambugu, MBChB, PhD +256-414-307291 akambugu@idi.co.ug
Uganda
 
NCT01782950
IDI
Yes
Infectious Diseases Institute, Makerere University
Makerere University
Not Provided
Principal Investigator: Barbara Castelnuovo, MBChB, PhD Infectious Diseases Institute
Makerere University
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP