Rifampin and Nevirapine Interactions in Young Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by The Miriam Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
The Miriam Hospital
ClinicalTrials.gov Identifier:
NCT01699633
First received: September 14, 2012
Last updated: October 11, 2012
Last verified: September 2012
  Purpose

Nevirapine is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV in children younger than 3 years old who have tuberculosis (TB) coinfection. However, there is very limited data on the drug-drug interactions between rifampin and nevirapine in children of this age group. The purpose of this study is to determine the effect of rifampin-containing anti-TB treatment on the blood levels of nevirapine in young children with HIV and TB coinfection. Also, the study will find out whether checking the genetic makeup of a child could help to determine the appropriate dose of nevirapine in the setting of concomitant anti-TB treatment.


Condition
Tuberculosis
HIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Rifampin-containing Anti-TB Therapy on Nevirapine Plasma Pharmacokinetics in HIV/TB Co-infected Children < 3 Years Old

Resource links provided by NLM:


Further study details as provided by The Miriam Hospital:

Primary Outcome Measures:
  • Area under time curve (AUC) of nevirapine [ Time Frame: At week of 4 of HIV therapy ] [ Designated as safety issue: No ]
    Compare nevirapine AUC0-12h 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


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 HIV 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 nevirapine 12-hour post-dose concentration (C12h) < 3000 ng/mL [ Time Frame: Week 4 of HIV therapy ] [ Designated as safety issue: No ]
    Relationship between clinical factors (weight, gender, nutritional status) as well as genetic factors (CYP2B6, CYP3A4 polymorphisms) and nevirapine C12h will be investigated

  • Time to HIV-1 RNA suppression below 50 copies/mL and change in CD4 cell count from baseline [ Time Frame: Up to week 24 of HIV therapy ] [ Designated as safety issue: No ]
    Relationship between nevirapine pharmacokinetics (AUC0-12h, C12h) and time to virologic suppression as well as increase in CD4 cell count from baseline in the combined study population

  • Peak concentration (Cmax) and concentration at 12-hours (C12h) post-dose of nevirapine [ Time Frame: At week 4 of therapy ] [ Designated as safety issue: No ]
    Compare nevirapine Cmax and C12h 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


Biospecimen Retention:   Samples With DNA

EDTA Plasma Whole blood DNA


Estimated Enrollment: 58
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 35 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children aged 3 to 35 months with HIV infection with or without TB

Criteria

Inclusion Criteria:

  1. HIV seropositive children with or without active TB
  2. Aged 3 to 35 months old
  3. Antiretroviral-naïve and meet criteria for initiation of antiretroviral therapy
  4. Are available for follow-up until achievement of a study endpoint like completion of study or discontinuation of HAART, and/or PK 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
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: NCT01699633

Contacts
Contact: Awewura Kwara, MD, MPH&TM 4017932463 akwara@lifespan.org
Contact: Sampson Antwi, MBChB +233265812061 antwisampson@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: NCT01699633     History of Changes
Other Study ID Numbers: PK-TBHIV02, R01HD071779
Study First Received: September 14, 2012
Last Updated: October 11, 2012
Health Authority: Ghana: Committee on Human Research

Keywords provided by The Miriam Hospital:
Drug-drug interactions
Drug-gene interactions
Nevirapine
Rifampicin
children

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Rifampin
Nevirapine
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 19, 2014