Pharmacokinetics of Anti-TB Drugs in HIV/TB Co-infected Children in Ghana

NCT01687504 | Unknown DMC

• 2 other identifiers: PK-PTBHIV01R01HD071779
• Study Type: observational
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (also known as TB) is a common infection and a major cause of death in children. Effective treatment using a combination of anti-tuberculosis (anti-TB) medications saves lives, but dosages of these medications are not well established in children. Several research studies have shown that the recommended dosages of the anti-TB medications in children do not lead to adequate blood levels to kill the bacteria in some children. This situation may lead to treatment failure and emergence of drug resistance. As a result, the world Health Organization (WHO) recently recommended increased dosages for all the TB medications in children. This study is being conducted to find out if the increased dosages of the anti-TB drugs are safe and lead to adequate drug levels in the blood of children with TB with or without HIV infection.

Conditions

Tuberculosis; HIV

Keywords

pharmacokinetics; children; HIV; Tuberculosis; Pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• Descriptive statistics of PK parameters (Cmax, Tmax, AUC0-8h) of rifampin, isoniazid, pyrazinamide and ethambutol in children with TB with and without HIV coinfection

  Week 4 of therapy

Secondary Outcomes (6)

• Frequency of liver enzymes elevations compare to baseline, skin rashes, nausea, vomiting and treatment discontinuation or modifications due to drug side effects in children with TB with and without HIV coinfection

  up to week 24

• Relationship between genetic polymorphisms of N-acetyltransferase type 2 (NAT2) enzyme and isoniazid plasma Cmax and AUC in Ghanaian children with TB with and without HIV

  Week 4 of therapy

• Relationship between genetic polymorphisms of SLCO1B1 transporter and rifampin plasma Cmax and AUC in Ghanaian children with TB with and without HIV

  week 4 of therapy

• Relationship between plasma Cmax and AUC of isoniazid, rifampin, ethambutol and pyrazinamide at week 4 of therapy and frequency of anti-TB treatment discontinuation or modification

  up to week 24

• Relationship between NAT2 acelator status, SLCO1B1 genotype status and anti-TB treatment completion, discontinuation or modification

  up to week 24

Eligibility Criteria

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

Study Population

Children aged 3 months to 14 years old with active tuberculosis with or with HIV coinfection

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.
• 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 (2)

• Horita Y, Alsultan A, Kwara A, Antwi S, Enimil A, Ortsin A, Dompreh A, Yang H, Wiesner L, Peloquin CA. Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00008-18. doi: 10.1128/AAC.00008-18. Print 2018 Sep.

  PMID: 29914960 DERIVED

• Antwi S, Yang H, Enimil A, Sarfo AM, Gillani FS, Ansong D, Dompreh A, Orstin A, Opoku T, Bosomtwe D, Wiesner L, Norman J, Peloquin CA, Kwara A. Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01701-16. doi: 10.1128/AAC.01701-16. Print 2017 Feb.

  PMID: 27855070 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

EDTA plasma for analysis of drug concentrations Whole blood DNA for for genotyping of drug metabolizing enzymes and transporters

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: September 11, 2012
• First Posted: September 19, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: October 11, 2012

Record last verified: 2012-09

Locations

GH (1)