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Pharmacokinetics of Anti-TB Drugs in HIV/TB Co-infected Children in Ghana

This study is currently recruiting participants.
Verified September 2012 by The Miriam Hospital
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The Miriam Hospital
ClinicalTrials.gov Identifier:
NCT01687504
First received: September 11, 2012
Last updated: October 10, 2012
Last verified: September 2012
History of Changes
  Purpose

Tuberculosis (also known as TB) is a common infection and a major cause of death in children. Effective treatment using a combination of anti-tuberculosis (anti-TB) medications saves lives, but dosages of these medications are not well established in children. Several research studies have shown that the recommended dosages of the anti-TB medications in children do not lead to adequate blood levels to kill the bacteria in some children. This situation may lead to treatment failure and emergence of drug resistance. As a result, the world Health Organization (WHO) recently recommended increased dosages for all the TB medications in children. This study is being conducted to find out if the increased dosages of the anti-TB drugs are safe and lead to adequate drug levels in the blood of children with TB with or without HIV infection.


Condition
Tuberculosis
HIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics and Safety of the WHO Recommended Increased Dosages of the First-line Anti-TB Medications in Children With TB and HIV/TB Coinfection

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Miriam Hospital:

Primary Outcome Measures:
  • Descriptive statistics of PK parameters (Cmax, Tmax, AUC0-8h) of rifampin, isoniazid, pyrazinamide and ethambutol in children with TB with and without HIV coinfection [ Time Frame: Week 4 of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of liver enzymes elevations compare to baseline, skin rashes, nausea, vomiting and treatment discontinuation or modifications due to drug side effects in children with TB with and without HIV coinfection [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
    The frequency of each drug side effects between children with TB and children with with HIV/TB confection on standard anti-TB therapy will be compared by chi-square test

  • Relationship between genetic polymorphisms of N-acetyltransferase type 2 (NAT2) enzyme and isoniazid plasma Cmax and AUC in Ghanaian children with TB with and without HIV [ Time Frame: Week 4 of therapy ] [ Designated as safety issue: No ]
    Genetic effect of each genetic variant on PK parameter will be estimated as odds ratio between carrier and non-carrier for each variant

  • Relationship between genetic polymorphisms of SLCO1B1 transporter and rifampin plasma Cmax and AUC in Ghanaian children with TB with and without HIV [ Time Frame: week 4 of therapy ] [ Designated as safety issue: No ]
    Genetic effect of each genetic variant on PK parameter will be estimated as odds ratio between carrier and non-carrier for each genetic variant

  • Relationship between plasma Cmax and AUC of isoniazid, rifampin, ethambutol and pyrazinamide at week 4 of therapy and frequency of anti-TB treatment discontinuation or modification [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
    Differences in mean Cmax and AUC of each drug between children who complete 6 months anti-TB therapy and those who require treatment modification due to drug side effects will be compared by t-test or non-parametric test. Note that treatment modification due to drug side effects is as per national TB treatment guidelines but no new interventions are prescribed in this observation study.

  • Relationship between NAT2 acelator status, SLCO1B1 genotype status and anti-TB treatment completion, discontinuation or modification [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
    Genetic effect of each genetic variant on treatment discontinuation or modification rates will be estimated as odds ratio between carrier and non-carrier for each variant. Note that treatment modification due to drug side effects is as per national TB treatment guidelines but no new interventions are prescribed in this observation study.

  • Relationship between body weight, gender, nutritional status and plasma Cmax and AUC of isoniazid, rifampin, ethambutol and pyrazinamide in Ghanaian children with TB with and without HIV [ Time Frame: up to week 4 of therapy ] [ Designated as safety issue: No ]
    Appropriate regression model will be used to test correlation between clinical factors and anti-TB drugs PK parameters


Biospecimen Retention:   Samples With DNA

EDTA plasma for analysis of drug concentrations Whole blood DNA for for genotyping of drug metabolizing enzymes and transporters


Estimated Enrollment: 106
Study Start Date: October 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Months to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children aged 3 months to 14 years old with active tuberculosis with or with HIV coinfection

Criteria

Inclusion Criteria:

  1. Children with active TB with or without HIV co-infection. Active TB diagnosis defined by clinical criteria consistent with active TB and/or a positive AFB smear or mycobacterial culture.
  2. Aged 3 months to 14 years old.
  3. Available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling.

Exclusion Criteria:

  1. Unable to obtain informed signed consent parent(s) or legal guardian.
  2. Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea.
  3. Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, AST and ALT > 2X upper limit of normal.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687504

Contacts
Contact: Awewura Kwara, MD, MPH&TM 4017932463 akwara@lifespan.org
Contact: Sampson Antwi, MBChB +233265812061 antwisampson10@yahoo.com

Locations
Ghana
Komfo Anokye Teaching Hospital Recruiting
Kumasi, Ghana
Contact: Sampson Antwi, MBChB     +233265812061     antwisampson@yahoo.com    
Contact: Anthony Enimil, MBChB     +233208164433     tenimil@live.com    
Sponsors and Collaborators
The Miriam Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Awewura Kwara, MD, MPH&TM The Miriam Hospital
  More Information

No publications provided

Responsible Party: The Miriam Hospital
ClinicalTrials.gov Identifier: NCT01687504     History of Changes
Other Study ID Numbers: PK-PTBHIV01, R01HD071779
Study First Received: September 11, 2012
Last Updated: October 10, 2012
Health Authority: Ghana: Ministry of Health

Keywords provided by The Miriam Hospital:
pharmacokinetics
children
HIV
Tuberculosis
Pharmacogenetics

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on March 03, 2013