Rifampin and Nevirapine Interactions in Young Children

This study is currently recruiting participants.
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
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
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014