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

Makerere University

Status and phase: Unknown; Phase 4

Conditions: AIDS With Tuberculosis

Treatments: Drug: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide

Study type: Interventional

Funder types: Other

Identifiers

NCT01782950

IDI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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400 participants in 1 patient group

anti-tuberculosis drugs

Other group

Description:

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

Treatment:

Drug: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide