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

April 10, 2015 updated by: Infectious Diseases Institute, Makerere University

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Kampala, Uganda, 256
        • Recruiting
        • Infectious Diseases Institute
        • Contact:
        • Principal Investigator:
          • Barbara Castelnuovo, MBChB, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
clinical outcome
Time Frame: At the end of treatment (6 months after enrolmet)
To investigate the association between serum concentrations of antituberculosis drugs and tuberculosis treatment response in HIV-TB-co-infected individuals.
At the end of treatment (6 months after enrolmet)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
To investigate the steady-state pharmacokinetic parameters of anti-TB drugs at different time-points over the course of TB-treatment
At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
Number of adverse events
Time Frame: 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
To assess the safety and tolerability of anti-TB drugs based on the WHO guidelines
2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
ART trough levels
Time Frame: At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
To correlate the effect of anti-TB drugs on plasma concentrations of efavirenz or protease inhibitors and vice versa.
At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
Isoniazid Cmax
Time Frame: At 2 weeks, 8 weeks and 24 weeks
To evaluate the effect of acetylator geno-and phenotype (NAT-2 gene) on isoniazid plasma concentrations and toxicity
At 2 weeks, 8 weeks and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Makerere University

Investigators

  • Principal Investigator: Barbara Castelnuovo, MD, PhD, Infectious Diseases Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Anticipated)

March 1, 2016

Study Completion (Anticipated)

March 1, 2016

Study Registration Dates

First Submitted

January 9, 2013

First Submitted That Met QC Criteria

February 1, 2013

First Posted (Estimate)

February 4, 2013

Study Record Updates

Last Update Posted (Estimate)

April 13, 2015

Last Update Submitted That Met QC Criteria

April 10, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDI

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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