NCT01637558

Brief Summary

The aims of this project are to:

  1. 1.To evaluate the pharmacokinetics of first line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) when applying the 2010 WHO/IUATLD dosing guidelines across pediatric populations (0-12 years of age, HIV infected and uninfected, and with varied nutritional status) in Cape Town, South Africa and Blantyre, Malawi.
  2. 2.To evaluate an 8-hourly weight band-based dosing strategy for lopinavir/ritonavir using the commercially available lopinavir/ritonavir (4:1 ratio) in children in South Africa receiving rifampicin-based antituberculosis treatment.
  3. 3.To evaluate the pharmacokinetics of nevirapine in children in Malawi receiving rifampicin-based antituberculosis treatment.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2012

Longer than P75 for phase_4

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 2, 2012

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 11, 2012

Completed
4 months until next milestone

Study Start

First participant enrolled

November 1, 2012

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2017

Completed
Last Updated

October 27, 2017

Status Verified

October 1, 2017

Enrollment Period

4.7 years

First QC Date

July 2, 2012

Last Update Submit

October 26, 2017

Conditions

TuberculosisHIV

Outcome Measures

Primary Outcomes (1)

  • Area under the concentration time curve (AUC) for rifampicin, isoniazid, pyrazinamide, ethambutol, lopinavir and nevirapine

    Population PK model-derived AUC's (in mg.h/L)for each of the first line anti-TB drugs, and for the substudies, lopinavir and nevirapine respectively.

    5 years

Study Arms (4)

Main TB cohort

NO INTERVENTION

Children with tuberculosis 0-12 years of age

Lopinavir/Ritonavir - Cases

EXPERIMENTAL

children 3-20 kg with tuberculosis and indication for LPV/r-based ART

Drug: 8 hourly LPV/r during TB treatment

Lopinavir/Ritonavir - Controls

EXPERIMENTAL

Children 3-20 kg on LPV/r-based ART; no TB

Drug: Lopinavir/Ritonavir

Nevirapine arm

EXPERIMENTAL

children with TB and indication for nevi rapine-based ART

Drug: Nevirapine

Interventions

8 hourly LPV/r during TB treatmentDRUG

8 hourly LPV/r during TB treatment

Lopinavir/Ritonavir - Cases
NevirapineDRUG
Nevirapine arm
Lopinavir/RitonavirDRUG
Lopinavir/Ritonavir - Controls

Eligibility Criteria

Age1 Month - 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • ALL STUDY PARTICIPANTS
  • Aged \< 12 years.
  • Weighing \> 1.5 kg and \< 30 kg.
  • Written informed permission of parent or legal guardian for their child to participate.
  • Absence of clear indication of unwillingness or refusal to participate, and in children \> 7 years of age, assent to participate.
  • No contraindications to PK sampling (children with obviously very poor venous access will not be included).
  • Able to comply with study visits and procedures including regular adherence to routine medication, and adherence to the study medication.
  • Enrollment will be deferred in children with acute severe illness which would likely jeopardize participation (such as illness causing severe respiratory impairment, acute severe diarrhea, acute central nervous system impairment, severe life threatening systemic illness, or other severe conditions requiring hospitalization which would jeopardize participation). Children may be enrolled after recovery from acute illness.
  • ADDITIONAL CRITERIA FOR THE MAIN TB COHORT AND SUBSTUDIES
  • Main TB cohort
  • LPV SUBSTUDY
  • CASES \& CONTROLS
  • Children in whom ART with a LPV/r-containing regimen is indicated, OR, Children established on a LPV/r-containing regimen.
  • ALT \< 5-times the upper limit of the normal range.
  • Children weighing 3.0 - 19.9 kg.
  • +9 more criteria

You may not qualify if:

  • Indication for increased or reduced doses of 1st-line antiTB drugs (e.g. marked hepatic or renal impairment, TB meningitis).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Queen Elizabeth Central Hospital

Blantyre, Malawi

Location

Red Cross Childrens Hospital

Cape Town, Western Cape, 7700, South Africa

Location

KIDCRU, Tygerberg Hospital, Department of Paediatrics and Child Health, Stellenbosch University, South Africa.

Cape Town, Western Cape, 7725, South Africa

Location

Desmond Tutu Centre

Cape Town, Western Cape, South Africa

Location

Related Publications (3)

  • Galileya LT, Wasmann RE, Chabala C, Rabie H, Lee J, Njahira Mukui I, Hesseling A, Zar H, Aarnoutse R, Turkova A, Gibb D, Cotton MF, McIlleron H, Denti P. Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis. PLoS Med. 2023 Nov 21;20(11):e1004303. doi: 10.1371/journal.pmed.1004303. eCollection 2023 Nov.

    PMID: 37988391DERIVED

  • Rabie H, Rawizza H, Zuidewind P, Winckler J, Zar H, Van Rie A, Wiesner L, McIlleron H. Pharmacokinetics of adjusted-dose 8-hourly lopinavir/ritonavir in HIV-infected children co-treated with rifampicin. J Antimicrob Chemother. 2019 Aug 1;74(8):2347-2351. doi: 10.1093/jac/dkz171.

    PMID: 31081020DERIVED

  • Bekker A, Schaaf HS, Draper HR, van der Laan L, Murray S, Wiesner L, Donald PR, McIlleron HM, Hesseling AC. Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2171-9. doi: 10.1128/AAC.02600-15. Print 2016 Apr.

    PMID: 26810651DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

NevirapineLopinavir

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

PyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidinonesPyrimidines

Study Officials

  • Helen M McIlleron, PhD

    University of Cape Town

    PRINCIPAL INVESTIGATOR

  • Heather Zar, PhD

    University of Cape Town

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Prof

Study Record Dates

First Submitted

July 2, 2012

First Posted

July 11, 2012

Study Start

November 1, 2012

Primary Completion

July 31, 2017

Study Completion

July 31, 2017

Last Updated

October 27, 2017

Record last verified: 2017-10

Locations

MA(1)ZA(3)