DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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:

Cmax

Number 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

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017