Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes
SOUTH
1 other identifier
interventional
400
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Feb 2013
Typical duration for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 9, 2013
CompletedStudy Start
First participant enrolled
February 1, 2013
CompletedFirst Posted
Study publicly available on registry
February 4, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2016
CompletedApril 13, 2015
April 1, 2015
3.1 years
January 9, 2013
April 10, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
clinical outcome
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 Outcomes (4)
Cmax
At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
Number of adverse events
2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
ART trough levels
At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation
Isoniazid Cmax
At 2 weeks, 8 weeks and 24 weeks
Study Arms (1)
anti-tuberculosis drugs
OTHERRifampicin, 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
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Infectious Diseases Institute
Kampala, Kampala, 256, Uganda
Related Publications (9)
Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC, Wells CD, Reingold AL, Kenyon TA, Moeti TL, Tappero JW. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009 Jun 15;48(12):1685-94. doi: 10.1086/599040.
PMID: 19432554BACKGROUNDWeiner M, Benator D, Burman W, Peloquin CA, Khan A, Vernon A, Jones B, Silva-Trigo C, Zhao Z, Hodge T; Tuberculosis Trials Consortium. Association between acquired rifamycin resistance and the pharmacokinetics of rifabutin and isoniazid among patients with HIV and tuberculosis. Clin Infect Dis. 2005 May 15;40(10):1481-91. doi: 10.1086/429321. Epub 2005 Apr 14.
PMID: 15844071BACKGROUNDGurumurthy P, Ramachandran G, Hemanth Kumar AK, Rajasekaran S, Padmapriyadarsini C, Swaminathan S, Bhagavathy S, Venkatesan P, Sekar L, Mahilmaran A, Ravichandran N, Paramesh P. Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother. 2004 Nov;48(11):4473-5. doi: 10.1128/AAC.48.11.4473-4475.2004.
PMID: 15504887BACKGROUNDNarita M, Hisada M, Thimmappa B, Stambaugh J, Ibrahim E, Hollender E, Ashkin D. Tuberculosis recurrence: multivariate analysis of serum levels of tuberculosis drugs, human immunodeficiency virus status, and other risk factors. Clin Infect Dis. 2001 Feb 1;32(3):515-7. doi: 10.1086/318490. Epub 2001 Jan 25.
PMID: 11170964BACKGROUNDGumbo T, Louie A, Deziel MR, Liu W, Parsons LM, Salfinger M, Drusano GL. Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob Agents Chemother. 2007 Nov;51(11):3781-8. doi: 10.1128/AAC.01533-06. Epub 2007 Aug 27.
PMID: 17724157BACKGROUNDSekaggya-Wiltshire C, Chirehwa M, Musaazi J, von Braun A, Buzibye A, Muller D, Gutteck U, Motta I, Calcagno A, Fehr JS, Kambugu A, Castelnuovo B, Lamorde M, Denti P. Low Antituberculosis Drug Concentrations in HIV-Tuberculosis-Coinfected Adults with Low Body Weight: Is It Time To Update Dosing Guidelines? Antimicrob Agents Chemother. 2019 May 24;63(6):e02174-18. doi: 10.1128/AAC.02174-18. Print 2019 Jun.
PMID: 30910890DERIVEDSekaggya-Wiltshire C, von Braun A, Lamorde M, Ledergerber B, Buzibye A, Henning L, Musaazi J, Gutteck U, Denti P, de Kock M, Jetter A, Byakika-Kibwika P, Eberhard N, Matovu J, Joloba M, Muller D, Manabe YC, Kamya MR, Corti N, Kambugu A, Castelnuovo B, Fehr JS. Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations. Clin Infect Dis. 2018 Aug 16;67(5):708-716. doi: 10.1093/cid/ciy179.
PMID: 29514175DERIVEDKwizera R, Parkes-Ratanshi R, Page ID, Sekaggya-Wiltshire C, Musaazi J, Fehr J, Castelnuovo B, Kambugu A, Denning DW. Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis. BMC Pulm Med. 2017 Nov 21;17(1):149. doi: 10.1186/s12890-017-0500-9.
PMID: 29162063DERIVEDSekaggya-Wiltshire C, Castelnuovo B, von Braun A, Musaazi J, Muller D, Buzibye A, Gutteck U, Henning L, Ledergerber B, Corti N, Lamorde M, Fehr J, Kambugu A. Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study. BMJ Open. 2017 Sep 18;7(9):e014679. doi: 10.1136/bmjopen-2016-014679.
PMID: 28928173DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Barbara Castelnuovo, MD, PhD
Infectious Diseases Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 9, 2013
First Posted
February 4, 2013
Study Start
February 1, 2013
Primary Completion
March 1, 2016
Study Completion
March 1, 2016
Last Updated
April 13, 2015
Record last verified: 2015-04