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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.
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
History of Changes
  Purpose

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.


Condition Intervention Phase
AIDS With Tuberculosis
 Drug: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes in HIV-tuberculosis Co-infected Ugandan Adults

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Makerere University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 400
Study Start Date: February 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01782950

Contacts
Contact: Andrew Kambugu, MBChB, PhD +256-414-307291 akambugu@idi.co.ug

Locations
Uganda
Infectious Diseases Institute Not yet recruiting
Kampala, Uganda
Principal Investigator: Barbara Castelnuovo, MBChB, PhD            
Sponsors and Collaborators
Makerere University
Investigators
Principal Investigator: Barbara Castelnuovo, MBChB, PhD Infectious Diseases Institute
  More Information

Publications:

Responsible Party: Infectious Diseases Institute, Principal Investigator, Makerere University
ClinicalTrials.gov Identifier: NCT01782950     History of Changes
Other Study ID Numbers: IDI
Study First Received: January 9, 2013
Last Updated: February 1, 2013
Health Authority: Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee

Keywords provided by Makerere University:
HIV
Tuberculosis
Antituberculosis drugs

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Antitubercular Agents
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
 Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antibiotics, Antitubercular
Enzyme Inhibitors
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013