Trial record 19 of 38 for:
" August 29, 2012":" September 28, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]
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
Information provided by (Responsible Party):
The Miriam Hospital
First received: September 11, 2012
Last updated: October 10, 2012
Last verified: September 2012
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.
||Observational Model: Cohort
Time Perspective: Prospective
||Pharmacokinetics and Safety of the WHO Recommended Increased Dosages of the First-line Anti-TB Medications in Children With TB and HIV/TB Coinfection
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 ]
Biospecimen Retention: Samples With DNA
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
EDTA plasma for analysis of drug concentrations Whole blood DNA for for genotyping of drug metabolizing enzymes and transporters
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||May 2017 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
||3 Months to 14 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Children aged 3 months to 14 years old with active tuberculosis with or with HIV coinfection
- 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.
- Aged 3 months to 14 years old.
- Available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling.
- Unable to obtain informed signed consent parent(s) or legal guardian.
- Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea.
- Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, AST and ALT > 2X upper limit of normal.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687504
The Miriam Hospital
||Awewura Kwara, MD, MPH&TM
||The Miriam Hospital
No publications provided
||The Miriam Hospital
History of Changes
|Other Study ID Numbers:
|Study First Received:
||September 11, 2012
||October 10, 2012
||Ghana: Ministry of Health
Keywords provided by The Miriam Hospital:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 16, 2014
Gram-Positive Bacterial Infections