Dose Reduction of Lopinavir in Children

This study has been completed.
Sponsor:
Collaborator:
Commission on Higher Education, Ministry of Education
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00887120
First received: April 21, 2009
Last updated: April 22, 2009
Last verified: April 2009

April 21, 2009
April 22, 2009
April 2007
January 2009   (final data collection date for primary outcome measure)
pharmacokinetics of standard vs low dose LPV/r [ Time Frame: 4 weeks after start ART ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00887120 on ClinicalTrials.gov Archive Site
efficacy and safety of standard and low dose LPV/r [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Dose Reduction of Lopinavir in Children
Pharmacokinetics and Efficacy of Low- or Standard-Dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children

To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.

To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children

In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).

Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).

Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing table
    • BW 6-7.9 kg: 1.5 mL oral q 12 hr
    • BW 8.0-16.9 kg: 2.0 ml oral q 12 hr
    • BW 17.0-19.9 kg: 2.5 ml oral q 12 hr
    • BW 20.0 - 24.9 kg: 3.0 ml oral q 12 hr
    • BW 25.0 - 29.9 kg: 3.5 ml oral q 12 hr
    • BW 30.0-34.9 kg: 4.0 ml oral q 12 hr
    • BW > 35 kg: 5.0 ml oral q 12 hr

    Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)

  • Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
    • BW 6-7.9 kg: 1.0 mL oral q 12 hr
    • BW 8.0-16.9 kg: 1.5 ml oral q 12 hr
    • BW 17.0-19.9 kg: 1.8 ml oral q 12 hr
    • BW 20.0 - 24.9 kg: 2.0 ml oral q 12 hr
    • BW 25.0 - 29.9 kg: 2.5 ml oral q 12 hr
    • BW 30.0-34.9 kg: 3.0 ml oral q 12 hr
    • BW > 35 kg: 3.5 ml oral q 12 h

    Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)

  • Active Comparator: 1
    Lopinavir/ritonavir standard dose + zidovudine and lamivudine
    Intervention: Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing table
  • Active Comparator: 2
    Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine
    Intervention: Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2009 Nov;64(5):1080-6. Epub 2009 Sep 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
February 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age from 2- 18 years old
  • Documented positive test for HIV-1 infection
  • PI-naïve
  • HIV RNA viral load > 1,000 copies
  • Written informed consent

Exclusion Criteria:

  • Active opportunistic infection
  • Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
  • Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
  • Pregnancy or lactating
  • Inability to understand the nature and extent of the study and the procedures required.
Both
2 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00887120
HIV-NAT045
No
Kiat Ruxrungtham, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
The HIV Netherlands Australia Thailand Research Collaboration
Commission on Higher Education, Ministry of Education
Principal Investigator: Kiat Ruxrungtham, MD Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
The HIV Netherlands Australia Thailand Research Collaboration
April 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP