Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes
Information source: Makerere University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: AIDS With Tuberculosis
Intervention: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Makerere University Official(s) and/or principal investigator(s): Barbara Castelnuovo, MD, PhD, Principal Investigator, Affiliation: Infectious Diseases Institute
Overall contact: Andrew Kambugu, MMED, Phone: +256-414-307000, Ext: 227, Email: akambugu@idi.co.ug
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.
Clinical Details
Official title: Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes in HIV-tuberculosis Co-infected Ugandan Adults
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: clinical outcome
Secondary outcome: CmaxNumber of adverse events ART trough levels Isoniazid Cmax
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Andrew Kambugu, MMED, Phone: +256-414-307000, Ext: 227, Email: akambugu@idi.co.ug
Infectious Diseases Institute, Kampala 256, Uganda; Recruiting Christine Sekaggya, MMed, Phone: +256312307000, Ext: 370, Email: csekaggya@idi.co.ug Barbara Castelnuovo, MBChB, PhD, Principal Investigator
Additional Information
Related publications: 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. Weiner 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. Epub 2005 Apr 14. Gurumurthy 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. Narita 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. Epub 2001 Jan 25. Gumbo 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. Epub 2007 Aug 27.
Starting date: February 2013
Last updated: April 10, 2015
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