Rifampin and Efavirenz Interactions in Older Children
This study is currently recruiting participants.
(see Contacts and Locations)
Verified September 2012 by The Miriam Hospital
Sponsor:
The Miriam Hospital
Collaborator:
Information provided by (Responsible Party):
The Miriam Hospital
ClinicalTrials.gov Identifier:
NCT01704144
First received: October 4, 2012
Last updated: October 16, 2012
Last verified: September 2012
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Purpose
Efavirenz is an essential component of HIV treatment in children aged 3 years or older on anti-tuberculosis (anti-TB) treatment. However, the appropriate efavirenz dose during anti-TB treatment remains unclear. Rifampin (an anti-TB drug) increases the activity of the drug metabolizing enzymes that breakdown efavirenz, which may lead to low blood levels of efavirenz and treatment failure during cotreatment. The drug-to-drug interactions between the HIV and anti-TB drugs also vary between individuals based on genetic factors. This study will investigate the effects of anti-TB treatment, as well as drug-gene interactions on the blood concentrations of efavirenz in children with HIV and TB infections. Such data could enhance optimization of efavirenz dosage or selection of alternate regimens in some children.
| Condition |
|---|
|
HIV Tuberculosis |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort Time Perspective: Prospective |
| Official Title: | Effect of Rifampin-containing Anti-TB Treatment on Efavirenz Pharmacokinetics in HIV/TB Co-infected Children Aged 3 - 14 Years |
Resource links provided by NLM:
Genetic and Rare Diseases Information Center resources:
Children's Interstitial Lung Disease
Tuberculosis
U.S. FDA Resources
Further study details as provided by The Miriam Hospital:
Primary Outcome Measures:
- Area under time curve from time 0-24 hours(AUC0-24h) of efavirenz [ Time Frame: At week of 4 of HIV therapy ] [ Designated as safety issue: No ]Compare efavirenz AUC0-24h between HIV-infected children without TB and those with TB on rifampin-containing anti-TB therapy in co-infected patients
Secondary Outcome Measures:
- Number of children with grade 3 or 4 liver enzymes elevations compared to baseline, new onset of skin rash, nausea, vomiting or treatment modification due to drug side effects [ Time Frame: up to week 24 of therapy ] [ Designated as safety issue: Yes ]Compare frequency of adverse events as a measure of safety and tolerability between HIV-infected children with and without TB coinfection
- Number of children with efavirenz 24-hour post-dose concentration (C24h) < 1000 ng/mL [ Time Frame: At week 4 of therapy ] [ Designated as safety issue: No ]Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6 516G>T, as well as CYP3A4, ABCB1, CAR and PXR polymorphisms) and efavirenz AUC0-24h and efavirenz C24h will be investigated
- Number of children who discontinue efavirenz therapy due to drug side effects [ Time Frame: Up to week 24 of HIV therapy ] [ Designated as safety issue: Yes ]Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6 polymorphisms) and treatment modification due to drug side effects in the combined study population
- Trough concentration (C24h) of efavirenz [ Time Frame: At week 4 of therapy ] [ Designated as safety issue: No ]Compare efavirenz C24h between HIV-infected children without TB and those with TB, as well as in the absence of and presence of rifampin-containing anti-TB therapy in co-infected patients
- AUC, Cmax and clearance of efavirenz on and off rifampin-containing anti-Tb therapy in HIV/TB co-infected patients [ Time Frame: at week 24 of therapy ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
EDTA plasma Whole blood DNA
| Estimated Enrollment: | 160 |
| 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 Years to 14 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Study Population
HIV-infected children with and with TB aged 3 to 14 years old
Criteria
Inclusion Criteria:
- 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
- Are 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:
- 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.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01704144
Please refer to this study by its ClinicalTrials.gov identifier: NCT01704144
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 antwisampson10@yahoo.com | |
| Contact: Anthony Enimil, MBChB +233208164433 tenimil@live.com | |
Sponsors and Collaborators
The Miriam Hospital
Investigators
| Principal Investigator: | Awewura Kwara, MD, MPH&TM | The Miriam Hospital |
More Information
No publications provided
| Responsible Party: | The Miriam Hospital |
| ClinicalTrials.gov Identifier: | NCT01704144 History of Changes |
| Other Study ID Numbers: | PK-PTBHIV03, R01HD071779 |
| Study First Received: | October 4, 2012 |
| Last Updated: | October 16, 2012 |
| Health Authority: | Ghana: Committee on Human Research |
Keywords provided by The Miriam Hospital:
|
Efavirenz rifampin Pharmacokinetics |
Drug-drug interactions Drug-gene interactions Children |
ClinicalTrials.gov processed this record on March 01, 2015