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TuberculosisNCT04972903

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

An observational study of Tuberculosis and Pulmonary, run by Institut National de la Santé Et de la Recherche Médicale, France at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 5 years
Conditions the study is for
Tuberculosis, Pulmonary
How many people
85 participants
Where
4 sitesin 2 countries
Study dates
8 Nov 2021to 22 Mar 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 5 years
  • All sexes
  • No healthy volunteers
  • Child

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-)

Who may be able to join

  • Gr1. HIV-infected children with SAM
  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-infection
  • SAM as defined by WHO at the time of starting TB treatment
  • Weight-for-height z-score (WHZ) < -3 SD,
Show all 46Show fewer
  • 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
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • 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
  • AND absence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian
  • Gr3. HIV-negative children with SAM
  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-negative
  • 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
  • Gr4. HIV-negative children without SAM
  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-negative
  • 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
  • AND absence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian
  • NON INCLUSION CRITERIA:
  • Very ill or moribund children unable to take drugs orally or requiring nasogastric drug intake
  • Severe anaemia (Hb < 6 g/dl),
  • Severe renal impairment (DAIDS grade 3 and above)
  • Severe hepatic impairment (DAIDS grade 3 and above)
  • Children on second line TB drugs

Who cannot join

None listed.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Uganda2 sites

  • Mulago National Referral Hospital

    Kampala

  • Mbarara Regional Hospital

    Mbarara

Other trials in Uganda

Zambia2 sites

  • The University Teaching Hospital

    Lusaka

  • Arthur Davison Children Hospital

    Ndola

Other trials in Zambia

About this study

Official title: Impact of Malnutrition on Pharmacokinetic of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in TB-HIV Co-infected Children

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.

Read the detailed description

Tuberculosis can worsen malnutrition and in turn malnutrition increases the risk of TB. HIV infection is prevalent in children with TB and SAM and is often associated with poor outcomes when present. TB alone is the leading cause of death of among HIV-infected children worldwide accounting for a third of all the death in this group.

In 2010, the WHO recommended increased dose for rifampicin (+50%), isoniazid (+100%), and pyrazinamide (+33%) based on PK data showing that plasma drug concentrations in children using standard adult dosages did not reach target levels. In children that are TB/HIV co-infected, drug-drug interactions between anti-TB drugs and antiretroviral drugs are of concern.

The investigators hypothesize that HIV-infection and SAM, each one on its own, may have an impact on TB drugs concentrations. Furthermore, SAM is frequent in children with HIV, and may affect the metabolism of anti-TB drugs and consequently result in low serum concentration.

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. It will be implemented in Uganda and Zambia. Children will also be enrolled from routine care for TB outside of the TB- Speed HIV and TB-Speed SAM studies.

Keywords
HIV, Childhood tuberculosis, Severe acute malnutrition, Pharmacokinetics, Pharmacodynamics
Medical subject headings
Tuberculosis, Severe Acute Malnutrition

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04972903
Study groupRoleWhat they receive
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-)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 6 months

  2. 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)

    Measured: 6 months

  3. 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)

    Measured: 6 months

Secondary outcomes (11)

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

    Cmax of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol in children with HIV infection on or off ART and children without HIV infection

    Measured: 6 months

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

    Cmin of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol in children with HIV infection on or off ART and children without HIV infection

    Measured: 6 months

  3. 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

    AUC of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol in children with HIV infection on or off ART and children without HIV infection

    Measured: 6 months

  4. 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

    Proportion of children with AUC24 and Cmax above the recommended threshold for Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol

    Measured: 6 months

  5. 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

    CL/F(Apparent total clearance of the drug from plasma) after oral administration of rifampicin, isoniazid, pyrazinamide, and ethambutol in HIV-infected children with TB.

    Measured: 6 months

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

    V/F (Apparent volume of distribution after administration) after oral administration of rifampicin, isoniazid, pyrazinamide, and ethambutol in HIV-infected children with TB.

    Measured: 6 months

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

    Ka (Absorption rate constant) after oral administration of rifampicin, isoniazid, pyrazinamide, and ethambutol in HIV-infected children with TB.

    Measured: 6 months

  8. Relationship between all-cause mortality in children with TB and SAM, and Peak plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol.

    Define the best Cmax plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol for treatment sucess.

    Measured: 6 months

  9. Relationship between all-cause mortality in children with TB and SAM, and the minimum plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol.

    Define the best Cmin plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol for treatment sucess.

    Measured: 6 months

  10. Relationship between all-cause mortality in children with TB and SAM, and Area Under the Curve plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol.

    Define the best AUC plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol for treatment sucess.

    Measured: 6 months

  11. Rifampicin protein binding in relation with malnutrition and albuminemia

    Proportion of protein bound rifampicin in children with SAM and association with albuminemia

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2021
  2. Study start8 Nov 2021
  3. Primary completion22 Mar 2022
  4. Study completion22 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04972903
Sponsor's protocol ID
C20-17
Status last verified
Jul 2024
First submitted
30 Jun 2021
Last updated
25 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

An observational study of Tuberculosis and Pulmonary, run by Institut National de la Santé Et de la Recherche Médicale, France at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Uganda, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of SAM on Peak plasma concentration of rifampicin, isoniazid, pyrazinamide, and ethambutol in children with TB (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04972903.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.

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