Impact of Malnutrition on Pharmacokinetic of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in TB-HIV Co-infected Children (TB-Speed TB-PK)

NCT04972903 | Completed

• 1 other identifier: C20-17
• Study Type: observational
• Target: 85
• Locations: 2 countries
• Sites: 4

Brief Summary

TB-Speed TB-PK is a cross-sectional PK study of anti-TB treatment nested in the TB-Speed HIV and TB-Speed SAM studies aiming at assessing the impact of malnutrition on PK of rifampicin, isoniazid, pyrazinamide, and ethambutol in TB-HIV co-infected children in Uganda and Zambia.

Conditions

Tuberculosis; Pulmonary

Keywords

HIV; Childhood tuberculosis; Severe acute malnutrition; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (3)

• Effect of SAM on Peak plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB

  Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol peak concentration (Cmax)

  6 months

• Effect of SAM on minimum plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB

  Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol minimum concentration (Cmin or C trough)

  6 months

• Effect of SAM on Area Under the Curve plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB

  Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol exposure (Area Under the Curve - AUC)

  6 months

Secondary Outcomes (11)

• Effect of HIV-infection and antiretroviral treatment on Peak plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB and SAM

  6 months

• Effect of HIV-infection and antiretroviral treatment on Minimum plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB and SAM

  6 months

• Effect of HIV-infection and antiretroviral treatment on Area Under the Curve plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB and SAM

  6 months

• WHO-based dosages will achieve rifampicin, isoniazid, pyrazinamide, and ethambutol drug concentrations above the target therapeutic concentrations in HIV-TB co-infected children with and without SAM

  6 months

• Effect of personnal parameters (nutritional parameters, HIV-infection, antiretroviral treatment, age, liver enzymes and NAT2 status) on CL/F of rifampicin, isoniazid, pyrazinamide, and ethambutol in HIV-infected children with TB

  6 months

Study Arms (4)

Group 1.HIV+/SAM+

Group 1. HIV-infected with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV+/SAM+)

Group 2. HIV+/SAM-

Group 2. HIV-infected without SAM (none of the 3 criteria above) (HIV+/SAM-)

Group 3. HIV-/SAM+

Group 3. HIV-negative with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV-/SAM+)

Group 4. HIV-/SAM-

Group 4. HIV-negative without SAM (none of the 3 criteria above) (HIV-/SAM-)

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Intensive PK of rifampicin, isoniazid, pyrazinamide, and ethambutol will be performed between 2 to 4 weeks of TB treatment in the following 4 groups of children receiving first-line anti-TB treatment: * Group (Gr) 1. HIV-infected with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV+/SAM+) * Gr2. HIV-infected without SAM (none of the 3 criteria above) (HIV+/SAM-) * Gr3. HIV-negative with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV-/SAM+) * Gr4. HIV-negative without SAM (none of the 3 criteria above) (HIV-/SAM-)

You may qualify if:

• Gr1. HIV-infected children with SAM
• Age 6 months to 5 years
• HIV-infection
• SAM as defined by WHO at the time of starting TB treatment
• Weight-for-height z-score (WHZ) \< -3 SD,
• OR MUAC \<11.5 cm or
• OR presence of bilateral pitting oedema of nutritional origin
• Ability to take drugs orally during the planned PK day
• Signed informed consent from parents or guardian
• Gr2. HIV-infected children without SAM
• Age 6 months to 5 years
• HIV-infection
• Absence of SAM as defined by WHO at the time of starting TB treatment
• Weight-for-height z-score (WHZ) \> -3 SD,
• AND MUAC \>11.5 cm or

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• National Agency for Research on AIDS and Viral Hepatitis (ANRS): collaborator

Study Sites (4)

Mulago National Referral Hospital

Kampala, Uganda

Location

Mbarara Regional Hospital

Mbarara, Uganda

Location

The University Teaching Hospital

Lusaka, Zambia

Location

Arthur Davison Children Hospital

Ndola, Zambia

Location

Related Links

• TB-Speed project official website

MeSH Terms

Conditions

Tuberculosis; Severe Acute Malnutrition

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Design

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

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 22, 2021
• Study Start: November 8, 2021
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2023
• Last Updated: February 25, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2); ZA (2)