Rifampin and Efavirenz Interactions in Older Children

NCT01704144 | Unknown DMC

• 2 other identifiers: PK-PTBHIV03R01HD071779
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; Tuberculosis

Keywords

Efavirenz; rifampin; Pharmacokinetics; Drug-drug interactions; Drug-gene interactions; Children

Outcome Measures

Primary Outcomes (1)

• Area under time curve from time 0-24 hours(AUC0-24h) of efavirenz

  Compare efavirenz AUC0-24h between HIV-infected children without TB and those with TB on rifampin-containing anti-TB therapy in co-infected patients

  At week of 4 of HIV therapy

Secondary Outcomes (5)

• 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

  up to week 24 of therapy

• Number of children with efavirenz 24-hour post-dose concentration (C24h) < 1000 ng/mL

  At week 4 of therapy

• Number of children who discontinue efavirenz therapy due to drug side effects

  Up to week 24 of HIV therapy

• Trough concentration (C24h) of efavirenz

  At week 4 of therapy

• AUC, Cmax and clearance of efavirenz on and off rifampin-containing anti-Tb therapy in HIV/TB co-infected patients

  at week 24 of therapy

Eligibility Criteria

• Age: 3 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected children with and with TB aged 3 to 14 years old

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Miriam Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Komfo Anokye Teaching Hospital

Kumasi, Ghana

RECRUITING

Related Publications (1)

• Kwara A, Yang H, Antwi S, Enimil A, Gillani FS, Dompreh A, Ortsin A, Opoku T, Bosomtwe D, Sarfo A, Wiesner L, Norman J, Alghamdi WA, Langaee T, Peloquin CA, Court MH, Greenblatt DJ. Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old. Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01657-18. doi: 10.1128/AAC.01657-18. Print 2019 Jan.

  PMID: 30397066 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

EDTA plasma Whole blood DNA

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Awewura Kwara, MD, MPH&TM

  The Miriam Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Awewura Kwara, MD, MPH&TM

CONTACT

4017932463; akwara@lifespan.org

Sampson Antwi, MBChB

CONTACT

+233265812061; antwisampson10@yahoo.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 11, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: October 17, 2012

Record last verified: 2012-09

Locations

GH (1)