ClinicalTrials.gov
ClinicalTrials.gov Menu

Rifampin and Efavirenz Interactions in Older Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01704144
Recruitment Status : Unknown
Verified September 2012 by The Miriam Hospital.
Recruitment status was:  Recruiting
First Posted : October 11, 2012
Last Update Posted : October 17, 2012
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The Miriam Hospital

Study Description
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 or disease
HIV Tuberculosis

  Show Detailed Description

Study Design
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Observational
Estimated Enrollment : 160 participants
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
Study Start Date : October 2012
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information


Outcome Measures
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Area under time curve from time 0-24 hours(AUC0-24h) of efavirenz [ Time Frame: At week of 4 of HIV therapy ]
    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 :
  1. 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 ]
    Compare frequency of adverse events as a measure of safety and tolerability between HIV-infected children with and without TB coinfection

  2. Number of children with efavirenz 24-hour post-dose concentration (C24h) < 1000 ng/mL [ Time Frame: At week 4 of therapy ]
    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

  3. Number of children who discontinue efavirenz therapy due to drug side effects [ Time Frame: Up to week 24 of HIV therapy ]
    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

  4. Trough concentration (C24h) of efavirenz [ Time Frame: At week 4 of therapy ]
    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

  5. 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 ]

Biospecimen Retention:   Samples With DNA
EDTA plasma Whole blood DNA

Eligibility Criteria
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
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:

  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. 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:

  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
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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
Go to 
Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: The Miriam Hospital
ClinicalTrials.gov Identifier: NCT01704144     History of Changes
Other Study ID Numbers: PK-PTBHIV03
R01HD071779 ( U.S. NIH Grant/Contract )
First Posted: October 11, 2012    Key Record Dates
Last Update Posted: October 17, 2012
Last Verified: September 2012

Keywords provided by The Miriam Hospital:
Efavirenz
rifampin
Pharmacokinetics
 Drug-drug interactions
Drug-gene interactions
Children

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Efavirenz
Rifampin
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
 Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers